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Toxicology of Chemical Carcinogens

  • Chapter
Low Dose Exposures in the Environment

Part of the book series: Wissenschaftsethik und Technikfolgenbeurteilung ((ETHICSSCI,volume 23))

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Abstract

The basic toxicodynamic principles of chemically and of radiation-induced carcinogenesis are largely identical. However, toxicokinetic factors of uptake, distribution, metabolism and elimination of chemical compounds lead to further complications. A chemical carcinogen may either act in the form of the parent compound, or, very frequently, in the form of an ultimately active metabolite. Hence, a complicated interplay of activating and inactivating enzyme systems must be considered in performing low-dose extrapolations. This chapter provides some outstanding examples of typical ways of argumentation.

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References

  • Abelson PH (1994) Risk assessment of low-level exposures. Science 265: 1507

    Article  Google Scholar 

  • Adamson RH, Thorgeirsson UP, Sugimura T (1996) Extrapolation of heterocyclic amine carcinogenesis data from rodents and nonhuman primates to humans. Arch Toxicol Suppl 18: 303–318

    Article  Google Scholar 

  • Adler ID, Andrae U, Kreis P, Neumann HG, Thier R, Wild D (2000) Recommendations for the categorization of germ cell mutagens. Int Arch Occup Environ Health 73: 428–432

    Article  Google Scholar 

  • Agency for Toxic Substances and Disease Registry — US Dept. of Health and Human Services [ATSDR] (1997) Toxicological Profile for Vinyl Chloride. ATSDR, Atlanta, GA

    Google Scholar 

  • Agency for Toxic Substances and Disease Registry (ATSDR) (1992) Toxicological profile for vinyl acetate. U.S. Public Health Service, U.S. Department of Health and Human Services, Atlanta, GA

    Google Scholar 

  • Albert RE, Sellakumar AR, Lashkin S, Kuschner M, Nelson M, Snyder CA (1982) Gaseous formaldehyde and hydrogen chloride induction of nasal cancer in the rat. J Natl Cancer Inst 68: 597–602

    Google Scholar 

  • Alexander FE, Patheal SL, Biondi A, Brandalise S, Cabrera ME, Chan LC, Chen Z, Cimino G, Cordoba JC, Gu LJ, Hussein H, Ishii E, Kamel AM, Labra S, Magalhaes IQ, Mizutani S, Petridou E, de Oliveira MP, Yuen P, Wiemels JL, Greaves MF (2001) Transplacental chemical exposure and risk of infant leukemia with MLL gene fusion. Cancer Res 61: 2542–2546

    Google Scholar 

  • Alexander J, Wallin H Home JA, Becher G (1989) 4-(2-amino-l-methylimidazo[4,5-b]pyrid-6-yl)phenyl sulphate — a major metabolite of the food mutagen 2-amino-l-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) in the rat. Carcinogenesis 10: 1543–1547

    Article  Google Scholar 

  • American Conference of Governmental Industrial Hygienists [ACGIH] (2001) TLVs and BEIs. [Documentation on the Threshold Limit Values and Biological Exposure Indices], 7th edition. American Conference of Governmental Industrial Hygienists, Cincinnati, OH

    Google Scholar 

  • Anderson KE, Carmella SG, Ye M, Bliss RL, Le C, Murphy L, Hecht SS (2001) Metabolites of a tobaccospecific lung carcinogen in nonsmoking women exposed to environmental tobacco smoke. J Natl Cancer Inst 93: 378–381

    Article  Google Scholar 

  • Andreola F, Fernandez-Salguero PM, Chiantore MV, Petkovich MP, Gonzalez FJ, De-Luca LM (1997) Aryl hydrocarbon receptor knockout mice (AHR-/-) exhibit liver retinoid accumulation and reduced retinoic acid metabolism. Cancer Res 57: 2835–2838

    Google Scholar 

  • Anwar WA, Khalil MM, Wild CP (1994) Micronuclei, chromosomal aberrations and aflatoxin-albumin adducts in experimental animals after exposure to aflatoxin Bl. Mutat Res 322: 61–67

    Article  Google Scholar 

  • Aoyama T, Gelboin HV, Gonzalez FJ (1990) Mutagenic activation of 2-amino-3-methyl-imidazo[4,5-f]quinoline by complementary DNA expressed human liver P450. Cancer Res 50: 2060–2063

    Google Scholar 

  • Appelman LM, Woutersen RA, Zwart A, Falke HE, Feron V (1988) One-year inhalation toxicity study of formaldehyde in male rats with a damaged or undamaged nasal mucosa. J Appl Toxicol 8: 85–90

    Article  Google Scholar 

  • Arand M, Mühlbauer R, Hengstler JG, Jäger E, Fuchs J, Winkler L, Oesch F, (1996) A multiplex polymerase chain reaction protocol for the simultaneous analysis of the glutathione S-trans-ferase GSTM1 and GSTT1 polymorphisms. Anal Biochem 236: 184–186

    Article  Google Scholar 

  • Argyris TS (1985) Promotion of epidermal carcinogenesis by repeated damage to mouse skin. Am J Indust Med 8:29–37

    Article  Google Scholar 

  • Bailey EA, Iyer RS Stone MP, Harris TM, Essigmann JM (1996) Mutational properties of the primary aflatoxin B1-DNA adduct. Proc Natl Acad Sci USA 93: 1535–1539

    Article  Google Scholar 

  • Bamberger J (2000) Vinyl acetate: Subchronic toxicity 90-day drinking water in rats and mice. In: E I du Pont de Nemours & Company, Haskell Laboratory for Toxicology and Industrial Medicine, DuPont-3978, Newark, DE

    Google Scholar 

  • Bank PA, Yao EF, Phelps CL, Harper PA, Denison MS (1992) Species-specific binding of transformed Ah receptor to a dioxin responsive transcriptional enhancer. Eur J Biochem 228: 85–94

    Google Scholar 

  • Bartsch H, Malaveille C, Barbin A, Planche G (1979) Mutagenic and alkylating metabolites of haloethylenes, chlorobutadienes, and dichlorobutenes produced by rodent or human liver tissues. Arch Toxicol 41: 249–277

    Article  Google Scholar 

  • Bartsch H, O’Neill IK, Schulte-Hermann R (1987) Relevance of N-nitroso compounds to human cancer: overview. In: Relevance of N-nitroso compounds for human cancer: exposures and mechanism, IARC Sci. Publ. 84: 5–10

    Google Scholar 

  • Bartsch R, Förderkunz S, Reuter U, Sterzl-Eckert H, Greim H (1998) Maximum workplace concentration values and carcinogenicity classification for mixtures. Environ Health Perspect 106 Suppl 6: 1291–1293

    Article  Google Scholar 

  • Batlle DC, Peces R, LaPointe MS, Ye M, Daugirdas JT (1993) Cytosolic free calcium regulation in response to acute changes in intracellular pH in vascular smooth muscle. Am J Physiol Cell Physiol 264: 932–943

    Google Scholar 

  • Bauman JW, Goldsworthy TL, Dunn CS, Fox TR (1995) Inhibitory effects of 2,3,7,8-tetra-chlorodibenzo-p-dioxin on rat hepatocyte proliferation induced by 2/3 partial hepatectomy. Cell Prolif 28: 437–451

    Article  Google Scholar 

  • Becher H, Steindorf K, Flesch-Janys D (1998) Quantitative cancer risk assessment for dioxins using an occupational cohort. Environ Health Perspect 106 Suppl 2: 663–670

    Google Scholar 

  • Bedford P, Fox BW (1981) The role of formaldehyde in methylene dimethanesulfonate-induced DNA cross-links and its relevance to cytotoxicity. Chem Biol Interact 38: 119–126

    Article  Google Scholar 

  • Beland FA, Fullerton NF, Smith BA, Poirier MC (1992) DNA adduct formation and aromatic amine tumourigenesis. Prog Clin Biol Res 37479–37492

    Google Scholar 

  • Belinsky SA, Foley JF, White CM, Anderson MW, Maronpot RR (1990) Dose-response relationship between O 6-methylguanine formation in Clara cells and induction of pulmonary neoplasia in the rat by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Cancer Res 50: 3772–37780

    Google Scholar 

  • Belinsky SA, Walker VE, Maronpot RR, Swenberg JA, Anderson MW (1987) Molecular dosimetry of DNA adduct formation and cell toxicity in rat nasal mucosa following exposure to the tobacco specific nitrosamine 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone and their relationship to induction of neoplasia. Cancer Res 47: 6058–6065

    Google Scholar 

  • Belinsky SA, White CM, Boucheron JA, Richardson FC, Swenberg JA, Anderson M (1986) Accumulation and persistence of DNA adducts in respiratory tissue of rats following multiple administrations of the tobacco specific carcinogen 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone. Cancer Res 46: 1280–1284

    Google Scholar 

  • Bergman K, Mueller L, Teigen SW (1996) The genotoxicity and carcinogenicity of paracetamol: a regulatory (re)view. In: Current issues in mutagenesis and carcinogenesis, No. 65. Mutat Res 349: 263–288

    Google Scholar 

  • Blair A Saracci R, Stewart PA, Hayes RB, Shy C (1990) Epidemiologic evidence on the relationship between formaldehyde and cancer. Scand J Work Environ Health 16: 381–393

    Article  Google Scholar 

  • Bogdanffy MS, Dreef-van der Meulen HC, Beems RB, Feron VJ, Cascieri TC, Tyler TR, Vinegar MB, Rickard RW (1994) Chronic toxicity and oncogenicity inhalation study with vinyl acetate in the rat and mouse. Fundam Appl Toxicol 23: 215–229

    Article  Google Scholar 

  • Bogdanffy MS, Gladnick LN, Kegelman T, Frame SR (1997) Four week inhalation cell proliferation study of the effects of vinyl acetate on rat nasal epithelium. Inhal Toxicol 9: 331–350

    Article  Google Scholar 

  • Bogdanffy MS, Plowchalk DR, Sarangapani R, Starr TB, Andersen ME (2000) Mode of action-based dosimeters for interspecies extrapolation of vinyl acetate inhalation risk. Inhal Toxicol 13:377–396

    Article  Google Scholar 

  • Bogdanffy MS, Randall HW, Morgan KT (1986) Histochemical localization of aldehyde dehydrogenase in the respiratory tract of the Fischer 344 rat. Toxicol Appl Pharmacol 82: 560–567

    Article  Google Scholar 

  • Bogdanffy MS, Randall HW, Morgan KT (1987) Biochemical quantitation and histochemical localization of carboxylesterase in the nasal passages of the Fischer 344 rat and B6C3F1 mouse. Toxicol Appl Pharmacol 88: 183–194

    Article  Google Scholar 

  • Bogdanffy MS, Sarangapani R, Kimbell JS, Frame SR, Plowchalk DR (1998) Analysis of vinyl acetate metabolism in rat and human nasal tissues by an in vitro gas uptake technique. Toxicol Sci 46: 235–246

    Google Scholar 

  • Bogdanffy MS, Sarangapani R, Plowchalk DR, Jarabek AM, Andersen ME (1999) A biologically-based risk assessment for vinyl acetate-induced cancer and noncancer toxicity. Toxicol Sci 51: 19–35

    Article  Google Scholar 

  • Bogdanffy MS, Taylor ML (1993) Kinetics of carboxylesterase-mediated metabolism of vinyl acetate. Drug Metab Dispos 21:1107–1111

    Google Scholar 

  • Bogdanffy MS, Tyler TR, Vinegar MB, Rickard RW, Carpanini FMB, Cascieri TC (1993) Chronic toxicity and oncogenicity study with vinyl acetate in the rat: In utero exposure in drinking water. Fund Appl Toxicol 23: 206–214

    Article  Google Scholar 

  • Bolt HM (1976) Probleme der Toxikologie von Sexualhormonen. Fortschr Med 94: 731–734

    Google Scholar 

  • Bolt HM (1978) Metabolie activation of halogenated ethylenes. In: Remmer H, Bolt HM, Bannasch P, Popper H (eds) Primary Liver Tumours. MTP Press, Lancaster, pp 285–294

    Google Scholar 

  • Bolt HM (1987) Experimental toxicology of formaldehyde. J Cancer Res Clin Oncol 113: 305–309

    Article  Google Scholar 

  • Bolt HM (1996) Quantification of endogenous carcinogens. The ethylene oxide paradox. Biochem Pharmacol 52: 1–5

    Article  Google Scholar 

  • Bolt HM (1997) Risiken durch Stoffe am Arbeitsplatz. Möglichkeiten der Quantifizierung des endogenen Risikos. Gefahrstoffe — Reinhaltung der Luft 57: 241–242

    Google Scholar 

  • Bolt HM (1998) Toxicological defence and susceptibility in relation to risk assessment: limit values in occupational risk management. EUROTOX Newsl 21(1): 17–20

    Google Scholar 

  • Bolt HM (2002) Occupational versus environmental and lifestyle exposures of children and adolescents in the European Union. Toxicol Lett 127: 121–126

    Article  Google Scholar 

  • Bolt HM, Filser J, Laib RJ, Ottenwälder H (1980) Binding kinetics of vinyl chloride and vinyl bromide at very low doses. Quantitative aspects of risk assessment in chemical carcinogenesis. Arch Toxicol Suppl 3: 129–142

    Article  Google Scholar 

  • Bolt HM, Filser JG (1983) Quantitative Aspekte der Kanzerogenität von Vinylbromid. Verh Dtsch Ges Arbeitsmedizin 23: 433–437

    Google Scholar 

  • Bolt HM, Gelbke HP, Kimmerle G, Laib RJ, Neumann HG, Norpoth KH, Pott F, Steinhoff D, War-denbach P (1988) Stoffe mit begründetem Verdacht auf krebserzeugendes Potential (Abschnitt III, Gruppe B der MAK-Werte-Liste): Probleme und Lösungsmöglichkeiten. Arbeitsmed SozialmedPräventivmed23: 139–144

    Google Scholar 

  • Bolt HM, Göbel P (1972) Formation of oestrogens from androgens by human subcutaneous adipose tissue in vitro. Horm Metab Res 4: 312–313

    Article  Google Scholar 

  • Bolt HM, Janning P, Michna H, Degen GH (2001) Comparative assessment of endocrine modulators with oestrogenic activity: I. Definition of a hygiene-based margin of safety (HBMOS) for xeno-oestrogens against the background of european developments. Arch Toxicol 74: 649–662

    Article  Google Scholar 

  • Bolt HM, Laib R, Filser JG, Ottenwälder H, Buchter A (1981) Vinyl chloride and related compounds: mechanisms of action on the liver. In: Berk PD, Chalmers TC (eds) Frontiers in liver disease. Thieme-Stratton, New York, pp 80–92

    Google Scholar 

  • Bolt HM, Leutbecher M (1997) A note on the physiological background of the ethylene oxide adduct 7(2-hydroxyethyl)guanine in DNA from human blood. Arch Toxicol 71: 719–721

    Article  Google Scholar 

  • Bolt HM, Roos PH, Thier R (2003) The cytochrome P450 isoenzyme CYP2E1 in the biological processing of industrial chemicals: consequences for occupational and environmental medicine. Int Arch Occup Environ Health 76: 174–185

    Google Scholar 

  • Bolton MG, Munoz A, Jacobson LP, Groopman JD, Maxuitenko YY, Roebuck BD, Kensler TW (1993) Transient intervention with oltipraz protects against aflatoxin-induced hepatic tumouri-genesis. Cancer Res 53: 3499–3504

    Google Scholar 

  • Boobis AR, Gooderham NJ, Edwards RJ, Murray S, Lynch AM, Yadollahi-Farsani M, Davies DS (1996) Enzymic and interindividual differences in the human metabolism of heterocyclic amines. Arch Toxicol Suppl 18: 286–302

    Article  Google Scholar 

  • Boucheron JA, Richardson FC, Morgan PH, Swenberg JA (1987) Molecular dosimetry of O 4-ethyldeoxythymidine in rats continuously exposed to diethylnitrosamine. Cancer Res 47: 1577–1581

    Google Scholar 

  • Bressac B, Kew M, Wands J, Ozturk M (1991) Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa. Nature 350: 429–431

    Article  Google Scholar 

  • Brown HR, Leininger JR (1992) Pathobiology of the aging rat, Vol. 1. ILSI Press, Washington, DC, pp 377–87

    Google Scholar 

  • Brown-Peterson NJ, Krol RM, Zhu Y, Hawkins WE (1999) N-nitrosodiethylamine initiation of carcinogenesis in Japanese medaka (Oryzias latipes): hepatocellular proliferation, toxicity, and neoplastic lesions resulting from short-term, low-level exposure. Toxicol Sci 50: 186–194

    Article  Google Scholar 

  • Brüning T, Bolt HM (2000) Renal toxicity and carcinogenicity of trichloroethylene: key results, mechamisms, and controversies. Crit Rev Toxicol 30: 253–285

    Article  Google Scholar 

  • Brusick D (1986) Genotoxic effects in cultured mammalian cells produced by low pH treatment conditions and increased ion concentrations. Environ Mutagen 8: 879–886

    Article  Google Scholar 

  • Buchmann A, Stinchcombe S, Korner W, Hagenmaier H, Bock KW (1994) Effects of 2,3,7,8-tetra-chloro- and 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin on the proliferation of preneoplastic liver cells in the rat. Carcinogenesis 15:1143–1150

    Article  Google Scholar 

  • Buchter A, Bolt HM, Filser J (1978) Pharmakokinetik und Karzinogenese von Vinylchlorid. Arbeitsmedizinische Risikobeurteilung. Verh Dtsch Ges Arbeitsmed 18:111–124

    Google Scholar 

  • Buetler TM, Bammler TK, Hayes JD, Eaton DL (1996) Oltipraz-mediated changes in aflatoxin B1 biotransformation in rat liver: Implications for human chemointervention. Cancer Res 56: 2306–2313

    Google Scholar 

  • Buetler TM, Slone D, Eaton DL (1992) Comparison of the aflatoxin B1-8,9-epoxide conjugating activities of two bacterially expressed alpha class glutathione S-transferase isozymes from mouse and rat. Biochem Biophys Res Commun 188: 597–603

    Article  Google Scholar 

  • Bundesanstalt für Arbeitsschutz und Arbeitsmedizin (BAuA) (1997) Verordnung zum Schutz vor gefährlichen Stoffen — Gefahrstoffverordnung und Anhänge. Schriftenreihe der Bundesanstalt für Arbeitsschutz und Arbeitsmedizin — Regelwerk Rw 14, Wirtschaftsverlag NW, Bremerhaven

    Google Scholar 

  • Bundesministerium für Jugend, Familie und Gesundheit [BMJFG] (1984) Formaldehyd. Ein gemeinsamer Bericht des Bundesgesundheitsamtes, der Bundesanstalt für Arbeitsschutz und des Umweltbundesamtes. Kohlhammer, Stuttgart

    Google Scholar 

  • Buonarati M, Felton JS (1990) Activation of 2-amino-l-methyl-6-phenylimidazo[4,5–6]pyridine (PhIP) to mutagenic metabolites. Carcinogenesis 11: 1133–1138

    Article  Google Scholar 

  • Busby WF, Wogan GN (1984) Aflatoxins. In: Chemical Carcinogens, Vol. 2. Am Chem Soc Monogr 182: 945–1136

    Google Scholar 

  • Buss P, Caviezel M, Lutz WK (1990) Linear dose-response relationship for DNA adducts in rat liver from chronic exposure to aflatoxin B1. Carcinogenesis 11: 2133–2135

    Article  Google Scholar 

  • Butterworth BE, Bogdanffy MS (1999) A comprehensive approach for integration of toxicity and cancer risk assessments. Reg Toxicol Pharmacol. 29: 23–36

    Article  Google Scholar 

  • Caldwell J (1992) Problems and opportunities in toxicity testing arising from species differences in xenobiotic metabolism. Toxicol Lett 64/65: 651–659

    Article  Google Scholar 

  • Capen CC (1997) Mechanistic data and risk assessment of selected toxic end points of the thyroid gland. Toxicol Pathol 25: 39–48

    Article  Google Scholar 

  • Casanova M, Deyo DF, Heck HD’A (1989) Covalent binding of inhaled formaldehyde to DNA in the nasal mucosa of Fischer 344 rats: analysis of formaldehyde and DNA by high-performance liquid chromatography and provisional pharmacokinetic interpretation. Fund Appl Toxicol 12: 397–417

    Article  Google Scholar 

  • Casanova M, Morgan KT, Gross EA, Moss OR, Heck, HD’A (1994) DNA-protein crosslinks and cell replication at specific sites in the nose of F344 rats exposed subchronically to formaldehyde. Fund Appl Toxicol 23: 525–536

    Article  Google Scholar 

  • Casanova-Schmitz M, Heck HD’A (1983) Metabolism of formaldehyde in the rat nasal mucosa in vivo. Toxicol Appl Pharmacol 70: 239–253

    Article  Google Scholar 

  • Casanova-Schmitz M, Starr TB, Heck HD’A (1984) Differentiation between metabolic incorporation and covalent binding in the labeling of macromolecules in the rat nasal mucosa and bone marrow by inhaled 3H- and 14C-formaldehyde. Toxicol Appl Pharmacol 76: 26–44

    Article  Google Scholar 

  • Chen CJ, Chen CW, Wu MM, Kuo TL (1992) Cancer potential in liver, lung bladder and kidney due to ingested inorganic arsenic in drinking water. Br J Cancer 66: 888–892

    Article  Google Scholar 

  • Chen CJ, Chuang YC, Lin TM, Wu HY (1985) Malignant neoplasms among residents of a Black-foot disease-endemic area in Taiwan: High-arsenic artesian well water and cancers. Cancer Res 45: 5895–5899

    Google Scholar 

  • Clemens MR, Einsele H, Frank H, Remmer H, Waller HD (1983) Volatile hydrocarbons from hydrogen peroxide-induced lipid peroxidation of erythrocytes and their cell compounds. Biochem Pharmacol 32: 3877–3878

    Article  Google Scholar 

  • Clewell HJ, Gentry PR, Gearhart JM, Allen BC, Andersen ME (2001) Comparison of cancer risk estimates for vinyl chloride using animal and human data with a PBPK model. Sci Total Environ 274: 37–66

    Article  Google Scholar 

  • Clewell HJ, Gentry PR, Gearhart JM, Allen BC, Anderson ME (1995) Considering pharmacokinetic and mechanistic information in cancer risk assessments for environmental contaminants: examples with vinyl chloride and trichloroethylene Chemosphere 31: 2561–2578

    Google Scholar 

  • Cohn MS, DiCarlo FJ, Turturro A, Ulsamer AG (1985) Letter to the Editor. Toxicol Appl Pharmacol 77: 363–364

    Article  Google Scholar 

  • Cole KE, Jones TW, Lipsky MM, Trump BF, Hsu IC (1988) In vitro binding of aflatoxin B1 and 2-acetylaminofluorene to rat, mouse and human hepatocyte DNA: the relationship of DNA binding to carcinogenicity. Carcinogenesis 9: 711–716

    Article  Google Scholar 

  • Commission of the European Communities (1987) Legislation on dangerous substances. Classification and labelling in the European Communities. Vol. I. Graham & Trotman, London

    Google Scholar 

  • Crebelli R (2000) Threshold-mediated mechanisms in mutagenesis: implications in the classification and regulation of chemical mutagens. Mutat Res 464: 129–135

    Article  Google Scholar 

  • Croy RG, Wogan GN (1981) Quantitative comparison of covalent aflatoxin-DNA adducts formed in rat and mouse livers and kidneys. J Natl Cancer Inst 66: 761–768

    Google Scholar 

  • Cushnir JR, Naylor S, Lamb JH, Farmer PB (1993) Tandem mass spectrometric approaches for the analysis of alkylguanines in human urine. Org Mass Spectrom 28: 552–558

    Article  Google Scholar 

  • Dalbey WE (1982) Formaldehyde and tumours in hamster respiratory tract. Toxicology 24: 9–14

    Article  Google Scholar 

  • Datta S, Talukder G, Sharma A (1986) Cytotoxic effects of arsenic in dietary oil primed rats. Sci Culture 52: 196–198

    Google Scholar 

  • Davis CD, Adamson RH, Snyderwine EG (1993) Studies on the mutagenic activation of heterocyclic amines by Cynomolgus monkey, rat and human microsomes show that Cynomolgus monkeys have a low capacity to TV-oxidize the quinoxaline-type heterocyclic amines. Cancer Lett 73: 95–104

    Article  Google Scholar 

  • Deese DE, Joyner RE (1969) Vinyl acetate: a study of chronic human exposure. Am Ind Hyg Assoc J 30: 449–57

    Google Scholar 

  • Degen GH, Bolt HM (2000) Endocrine disruptors: update on xenoestrogens. Int Arch Occup Environ Health 73: 433–41

    Article  Google Scholar 

  • Degen GH, Janning P, Diel P, Michna H, Bolt HM (2002) Transplacental transfer of the phytoestrogen daidzein in DA/Han rats. Arch Toxicol 76: 23–9

    Article  Google Scholar 

  • Deutsche Forschungsgemeinschaft [DFG] (1999a) Quecksilber und organische Quecksilberverbindungen. In: Greim H (ed) Gesundheitsschädliche Arbeitsstoffe, toxikologisch-arbeitsmedizinische Begründungen von MAK-Werten, 28. Lieferung. Wiley-VCH, Weinheim

    Google Scholar 

  • Deutsche Forschungsgemeinschaft [DFG] (1999b) Styrol, Nachtrag 1998. In: Greim H (ed) Gesundheitsschädliche Arbeitsstoffe, toxikologisch-arbeitsmedizinische Begründungen von MAK-Werten, 28. Lieferung. Wiley-VCH, Weinheim

    Google Scholar 

  • Deutsche Forschungsgemeinschaft [DFG] (2000) Blei und seine anorganischen Verbindungen, außer Bleiarsenat und Bleichromat In: Greim H (ed) Gesundheitsschädliche Arbeitsstoffe, toxikologisch-arbeitsmedizinische Begründungen von MAK-Werten, 31. Lieferung. Wiley-VCH, Weinheim

    Google Scholar 

  • Deutsche Forschungsgemeinschaft [DFG] (2001) List of MAK and BAT values 2001. Maximum concentrations and biological tolerance values at the workplace, Report No. 37. Wiley-VCH, Weinheim

    Google Scholar 

  • Deutsche Forschungsgemeinschaft [DFG] (2002) Arsen und anorganische Arsenverbindungen. In: Greim H (ed) Gesundheitsschädliche Arbeitsstoffe: toxikologisch-arbeitsmedizinische Begründungen von MAK-Werten, 35. Lieferung. Wiley-VCH, Weinheim, pp 1–50

    Google Scholar 

  • Doolittle DJ, Furlong JW, Butterworth BE (1985) Assessment of chemically induced DNA repair in primary cultures of human bronchial epithelial cells. Toxicol Appl Pharmacol 79: 28–38

    Article  Google Scholar 

  • Dunning AM, Healey CS, Pharoah PD, Teare MD, Ponder BA, Easton DF (1999) A systematic review of genetic polymorphisms and breast cancer risk. Cancer Epidemiol Biomarkers Prev (10): 843–854

    Google Scholar 

  • Eastern Research Group (1997) Report on the expert panel on arsenic carcinogenicity: review and workshop. Prepared by Eastern Research Group, Lexington, MA, for the National Center for Environmental Assessment, Washington, DC, EPA contract no. 68-C6–0041

    Google Scholar 

  • Eaton DL, Gallagher EP (1994) Mechanism of aflatoxin carcinogenesis. Annu Rev Pharmacol Toxicol 34: 135–172

    Article  Google Scholar 

  • Eberhard DC (1991) Species differences in the toxicity and cytochrome P450 IIIA-dependent metabolism of digitoxin. Mol Pharmacol 40: 859–867

    Google Scholar 

  • Edwards RJ, Murray BP, Murray S, Schultz T, Neubert D, Gant TW, Thorgeirsson SS, Boobis AR, Davies DS (1994) Contribution of CYP1A1 and CYP1A2 to the activation of heterocyclic amines in monkeys and human. Carcinogenesis 15: 829–836

    Article  Google Scholar 

  • Ehrenberg L, Osterman-Golkar S, Segerbäck D, Svensson K, Calleman CJ (1977) Evaluation of genetic risks of alkylating agents. III. Alkylation of hemoglobin after metabolic conversion of ethene to ethene oxide in vivo. Mutat Res 45: 175–184

    Google Scholar 

  • Essigmann JM, Croy RG, Nadzan AM, Busby WF, Reinhold VN, Buchi G, Wogan GN (1977) Structural identification of the major DNA adduct formed by Aflatoxin B1 in vitro. Proc Natl Acad Sci USA 74: 1870–1874

    Article  Google Scholar 

  • European Union (2002) European Risk Assessment Report. Acrylamide. CAS No: 79–06-1, EINECS No: 201–173-7, Office for Official Publications of the European Communities, Luxembourg

    Google Scholar 

  • Faustman EM, Silbernagel SM, Fenske RA, Burbacher TM, Ponce RA (2000) Mechanisms underlying children’s susceptibility to environmental toxicants. Environ Health Perspect 108 Suppl 1: 13–21

    Google Scholar 

  • Fedtke N, Wiegand HJ (1990) Hydrolysis of vinyl acetate in human blood. Arch Toxicol 64: 428–429

    Article  Google Scholar 

  • Fernandez-Salguero P, Pineau T, Hilbert DM, McPhail T, Lee SS, Kimura S, Nebert DW, Rudikoff S, Ward JM, Gonzalez FJ (1995) Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor. Science 268: 722–726

    Article  Google Scholar 

  • Fernandez-Salguero PM, Hilbert DM, Rudikoff S, Ward JM, Gonzalez F J (1996) Aryl-hydrocarbon receptor-deficient mice are resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity. Toxicol Appl Pharmacol 140: 173–179

    Article  Google Scholar 

  • Feron VJ, Hendriksen CFM, Speek AJ, Til HP, Spit BJ (1981) Lifespan oral toxicity study of vinyl chloride in rats. Food Cosmet Toxicol 19: 317–333

    Article  Google Scholar 

  • Filser JG (1992) The closed chamber technique — uptake, endogenous production, excretion, steady-state kinetics and rates of metabolism of gases and vapors. Arch Toxicol 66: 1–10

    Article  Google Scholar 

  • Filser JG, Bolt HM (1984) Inhalation toxicokinetics based on gas uptake studies. VI. Comparative evaluation of ethylene oxide and butadiene monoxide as exhaled reactive metabolites of ethylene and 1,3-butadiene in rats. Arch Toxicol 55: 219–223

    Article  Google Scholar 

  • Filser JG, Kreuzer PE, Greim H, Bolt HM (1994) New scientific arguments for regulation of ethylene oxide residues in skin-case products. Arch Toxicol 68: 401–405

    Article  Google Scholar 

  • Fingerhut MA, Halperin WE, Marlow DA, Piacitelli LA, Honchar PA, Sweeney MH, Greife AL, Dill PA, Steenland K, Suruda AJ (1991) Cancer mortality in workers exposed to 2,3,7,8-tetra-chlorodibenzo-p-dioxin. N Engl J Med 324: 212–218

    Article  Google Scholar 

  • Finnish Institute of Occupational Health (1995) Työhygieenisten mittausten rekisteri [Registry of Industrial Hygiene Measurements] (Fin.). In: European Foundation for the Improvement of Living and Working Conditions (ed) The European health and safety database (HASTE) -Summaries of descriptions of systems for monitoring health and safety at work. Office for Official Publications of the European Communities, Luxemburg. Also available at http://192.58.80.9/e/eu/haste/index.htm

    Google Scholar 

  • Föst U, Marczynski M, Kasemann R, Peter H (1989) Determination of 7-(2-hydroxyethyl)guanine with gas chromatograph/mass spectrometry as a parameter for genotoxicity of ethylene oxide. Arch Toxicol Suppl 13: 250–253

    Article  Google Scholar 

  • Foster PL, Eisenstadt E, Miller JH (1983) Base substitution mutations induced by metabolically activated Aflatoxin B1. Proc Natl Acad Sci USA 80: 2695–2698

    Article  Google Scholar 

  • Fox AJ, Collier PF (1977) Mortality experience of workers exposure to vinyl chloride monomer in the manufacture of polyvinyl chloride in Great Britain. Br J Ind Med 34: 1–10

    Google Scholar 

  • Frank H, Hintze T, Remmer H (1980) Volatile hydrocarbons in breath, an indication for peroxida-tive degradation of lipids. In: Kolb B (ed) Applied head-space gas chromatography. Heyden, London, pp 155–164

    Google Scholar 

  • Fraser I (2001) Butadiene — progress under the European Union existing substances regulation. Chem Biol Interact 136: 103–108

    Article  Google Scholar 

  • Friedman M, Dulak L, Stedham M (1995) A lifetime oncogenicity study in rats with acrylamide. Fundam Appl Toxicol 27: 95–105

    Article  Google Scholar 

  • Frighi V, Ng LL, Lewis A, Dhar H (1991) Na+/H+ antiport and buffering capacity in human polymorphonuclear and mononuclear leukocytes. Clin Sci 80: 95–99

    Google Scholar 

  • Fuchs J, Wullenweber U, Hengstler JG, Bienfait HG, Hiltl G, Oesch F (1994) Genotoxic risk for humans due to work place exposure to ethylene oxide: remarkable individual differences in susceptibility. Arch Toxicol 68: 343–348

    Article  Google Scholar 

  • Furst A (1983) A new look at arsenic carcinogenesis. In: Lederer W, Fensterheim R (eds) Arsenic: industrial, biomedical, and environmental perspective. Van Nostrand Reinhold, New York, pp 151–163

    Google Scholar 

  • Gallagher EP, Wienkers LC, Stapleton PL, Kunze KL, Eaton DL (1994) Role of human microsomal and human complementary DNA-expressed cytochrome P450 1A2 and cytochrome P450 3 A4 in the bioactivation of aflatoxin B1. Cancer Res 54: 101–108

    Google Scholar 

  • Garner RC, Wright CM (1975) Binding of [14C]aflatoxin B, to cellular macromolecules in the rat and hamster. Chem Biol Interact 11: 123–131

    Article  Google Scholar 

  • Gehring PJ, Watanabe PG, Park CN (1978) Resolution of dose-response toxicity data for chemicals requiring metabolic activation. Example: vinyl chloride. Toxicol Appl Phramacol 44: 581–591

    Article  Google Scholar 

  • Gehring PJ, Watanabe PG, Park CN (1979) Risk of angiosarcoma in workers exposed to vinyl chloride as predicted from studies in rats. Toxicol Appl Pharmacol 49: 15–21

    Article  Google Scholar 

  • Gelfand VI, Scholey JM (1992) Cell biology. Every motion has its motor. Nature 359(6395): 480–482

    Article  Google Scholar 

  • Gerhardsson de Verdier M, Hagman U, Peters RK, Steineck G, Overvik E (1991) Meat cooking methods and colorectal cancer: a case- referent study in Stockholm. Int J Cancer 49: 520–525

    Article  Google Scholar 

  • Geyer HJ, Schramm K-W, Scheunert I, Schughart K, Buters J, Wurst W, Greim H, Kluge R, Steinberg CEW, Kettrup A, Madhukar B, Olso JR, Gallo MA (1997) Considerations on genetic and environmental factors that contribute to resistance or sensitivity of mammals including humans to toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Ecotoxicol Environ Safety 36: 213–230

    Article  Google Scholar 

  • Gielen JE, Goujon FM, Nebert DW (1972) Genetic regulation of aryl hydrocarbon hydroxylase induction. II. Simple Mendelian expression in mouse tissues in vivo. J Biol Chem 247: 1125–1137

    Google Scholar 

  • Gilli G, Bugliosi EH, Schiliro T (2001) Human immunological response against the molecular adduct F-HSA as biomarker of occupational and environmental exposure to formaldehyde. EPI Marker 5(3): 1–4

    Google Scholar 

  • Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Ascherio A, Willett WC (1994) Intake of fat, meat and fiber in relation to risk of colon cancer in men. Cancer Res 54: 2390–2397

    Google Scholar 

  • Goldberg M, Unger M (2000) Lung cancer. Diagnostic tools. Chest Surg Clin N Am 10(4): 763–79

    Google Scholar 

  • Goldman M (1996) Cancer risk of low-level exposure. Science 271: 1821–1822

    Article  Google Scholar 

  • Grafstrom RC, Fornace A, Harris CC (1984) Repair of DNA damage caused by formaldehyde in human cells. Cancer Res 44: 4323–4327

    Google Scholar 

  • Guengerich FP (1996) Metabolic control of carcinogens. In: Hengstler JG, Oesch F (eds) Control mechanisms of carcinogens. Publishing House of the Editors, Mainz

    Google Scholar 

  • Guengerich FP, Johnson WW, Shimada T, Ueng YF, Yamazaki H, Langouet S (1998) Activation and detoxication of Aflatoxin B1. Mutat Res 402: 121–128

    Article  Google Scholar 

  • Gupta RS, Chopra A, Stetsko DK (1986) Cellular basis for the species differences in sensitivity to cardiac glycosides (digitalis). J Cell Physiol. 127: 197–206

    Article  Google Scholar 

  • Gurtoo HL, Motycka L (1976) Effect of sex differences on the in vitro and in vivo metabolism of aflatoxin B1 by the rat. Cancer Res 36: 4663–4671

    Google Scholar 

  • Halvorson MR, Noffsinger JK, Peterson CM (1993) Studies of whole blood-associated acetaldehyde levels in teetotallers. Alcohol 10: 409–413

    Article  Google Scholar 

  • Hang B, Medina M, Fraenkel-Conrat H, Singer B (1998) A 55 kDa protein isolated from human cells shows DNA glycosylase activity toward 3,N 4-ethenocytidine and the G/T mismatch. Proc Natl Acad Sci USA 95: 13561–13566

    Article  Google Scholar 

  • Hankinson O, Bacsi SG, Fukunaga BN, Kozak KR, McNulty SE, Minehart E, Probst MR, Reisz-Porszasz S, Sun W, Zhang J (1996) Role of the aryl hydrocarbon receptor in carcinogenesis. In: Hengstler JG, Oesch F (eds) Control Mechanisms of Carcinogenesis. Publishing House of the Editors, Mainz

    Google Scholar 

  • Harris CC, Grafstrom RC, Lechner JF, Autrup H (1983) In: Banbury Report No. 12, Nitrosamines and human cancer. Cold Spring Harbor, NY, p 121

    Google Scholar 

  • Hartwig A, Schwerdtle T (2000) Interactions by carcinogenic metal compounds with DNA repair processes: toxicological implications. Toxicol Lett 127: 47–54

    Article  Google Scholar 

  • Haseman JK, Haily JR (1997) An update of the National Toxicology Program database on nasal carcinogens. Mutat Res 380: 3–11

    Article  Google Scholar 

  • Hayes JD, Judah DJ, McLellan LI, Kerr LA, Peacock SD, Neal GE (1991) Ethoxyquin-induced resistance to aflatoxin B1 in the rat is associated with the expression of a novel alpha-class glutathione S-transferase subunit Yc2, which possesses high catalytic activity for aflatoxin B,-8,9-epoxide. Biochem J 279: 385–398

    Google Scholar 

  • Hayes JD, Nguyen T, Judah DJ, Petersson DG, Neal GE (1994) Cloning of cDNAs from fetal rat liver encoding glutathione S-transferase Yc polypeptides: the Yc2 subunit is expressed in adult rat liver resistant to the hepatocarcinogen aflatoxin B1. J Biol Chem 269: 20707–20717

    Google Scholar 

  • Hays SM, Aylward LL, Karch NJ, Paustenbach DJ (1997) The relative susceptibility of animals and humans to the carcinogenic hazard posed by exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin: an analysis using standard and internal measures of dose. Chemosphere 34: 1507–1522

    Article  Google Scholar 

  • Hazelton GA, Klaassen CD (1988) UDP-glucuronosyltransferase activity toward digitoxigenin-monodigitoxide. Differences in activation and induction properties in rat and mouse liver. Drug Metab Dispos 16:30–36

    Google Scholar 

  • Hengstler JG, Arand M, Herrero ME, Oesch F. (1998) Polymorphisms of N-acetyltransferases, glutathione S-transferases, microsomal epoxide hydrolase and sulfotransferases: influence on cancer susceptibility. Recent results. Cancer Res 154: 47–85

    Article  Google Scholar 

  • Hengstler JG, Bogdanffy MS, Bolt HM, Oesch F (2003) Challenging dogma: thresholds for geno-toxic chemicals? The case of vinyl acetate. Annu Rev Pharmacol Toxicol 43: 485–520

    Article  Google Scholar 

  • Hengstler JG, Kett A, Arand M, Oesch-Bartlomowicz B, Oesch F, Pilch H, Tanner B (1998) Glutathione S-transferase 77 and M1 gene defects in ovarian carcinoma. Cancer Lett 130: 43–48

    Article  Google Scholar 

  • Hengstler JG, Lange J, Kett A, Dornhofer N, Meinert R, Arand M, Knapstein PG, Becker R, Oesch F, Tanner B (1999b) Contribution of c-erbB-2 and topoisomerase IIa to chemoresistance in ovarian cancer. Cancer Res 59: 3206–3214

    Google Scholar 

  • Hengstler JG, Utesch D, Steinberg P, Ringel M, Swales N, Biefang K, Platt KL, Diener B, Böttger T, Fischer T, Oesch F (2000) Cryopreserved primary hepatocytes as an in vitro model for the evaluation of drug metabolism and enzyme induction. Drug Metab Rev 32: 81–118

    Article  Google Scholar 

  • Hengstler JG, Van der Burg B, Steinberg P, Oesch F (1999) Interspecies differences in cancer susceptibility and toxicity. Drug Metab Rev 31: 917–970

    Article  Google Scholar 

  • Henningsen U, Schliwa M (1997) Reversal in the direction of movement of a molecular motor. Nature 389: 93–96

    Article  Google Scholar 

  • Herrero ME, Arand M, Hengstler JG, Oesch F (1997) Recombinant expression of human microsomal epoxide hydrolase protects V79 Chinese hamster cells from styrene oxide- but not from ethylene oxide-induced DNA strand breaks. Environ Mol Mutagen 30: 429–439

    Article  Google Scholar 

  • Hirokawa N (1996) The molecular mechanism of organelle transport along microtubules: the identification and characterization of KIFs (kinesin superfamily proteins). Cell Struct Funct 21: 357–367

    Article  Google Scholar 

  • Homann N, Karkkainen P, Koivisto T, Nosova T, Jokelainen K, Salaspuro M (1997) Effects of acetaldehyde on cell regeneration and differentiation of the upper gastrointestinal tract mucosa. J Natl Cancer Instit 89: 1692–1697

    Article  Google Scholar 

  • Horn EP, Tucker MA, Lambert G, Silverman D, Zametkin D, Sinha R, Hartge T, Landi MT, Caporaso NE (1995) A study of gender-based cytochrome P450 1A2 variability: a possible mechanism for the male excess of bladder cancer. Cancer Epidemiol Biomarkers Prev 4: 529–533

    Google Scholar 

  • Hsu IC, Metcalf RA, Sun T, Welsh JA, Wang NJ, Harris CC (1991) Mutational hotspot in the p53 gene in human hepatocellular carcinomas. Nature 350: 427–428

    Article  Google Scholar 

  • Imbus HR (1988) A review of regulatory risk assessment with formaldehyde as an example. Regul Toxicol Pharmacol 8: 356–366

    Article  Google Scholar 

  • Ingelman-Sundberg M, Daly AK, Oscarson M, Nebert DW (2000) Human cytochrome P450 (CYP) genes: recommendations for the nomenclature of alleles. Pharmacogenetics 10(1): 91–93

    Article  Google Scholar 

  • Innes JRM, Ulland BM, Valerio MG (1969) Bioassay of pesticides and industrial chemicals for tumorigenicity in mice: a preliminary note. J Natl Cancer Inst USA 42: 1101–1114

    Google Scholar 

  • International Agency for Research on Cancer [IARC] (1980) Some metals and metallic compounds. IARC Monogr Eval Carcinog Risk Chem Hum 23: 1–415

    Google Scholar 

  • International Agency for Research on Cancer [IARC] (1985) Allyl compounds, aldehydes, epoxides and peroxides. IARC Monogr Eval Carcinog Risks Hum 36

    Google Scholar 

  • International Agency for Research on Cancer [IARC] (1987) Overall evaluation of carcinogenicity: An updating of IARC Monographs Volumes 1 to 42 IARC Monogr Eval Carcinog Risks Hum Suppl 7

    Google Scholar 

  • International Agency for Research on Cancer [IARC] (1997) Polychlorinated dibenzo-para-dioxins and polychlorinated dibenzofurans. IARC Monogr Eval Carcinog Risks Hum 69 1–666

    Google Scholar 

  • International Agency for Research on Cancer [IARC] (1999) Hormonal Contraception and postmenopausal hormonal therapy. IARC Monogr Eval Carcinog Risks Hum 72: 1–660

    Google Scholar 

  • International Agency for Research on Cancer [IARC] (2001) Some Thyrotropic Agents. IARC Monogr Eval Carcinog Risks Hum 79: 1–763

    Google Scholar 

  • International Programme on Chemical Safety, World Health Organisation [IPCS-WHO] (1999): Vinyl Chloride, IPCS Environmental Health Criteria 215, International Programme on Chemical Safety, World Health Organisation, Geneva

    Google Scholar 

  • International Technology Corporation (1992) Exposure to volatile components of polyvinyl, acetate (PVA) emulsion paints during application and drying, National. Paint and Coating Association, Vinyl Acetate Toxicology Group, Washington, DC

    Google Scholar 

  • Isfort RJ, Cody DB, Asuith TN, Ridder GM, Stuard SB, LeBoeuf RA (1993) Induction of protein phosphorylation, protein synthesis, immediate-early-gene expression and cellular proliferation by intracellular pH modulation. Eur J Biochem 213: 349–357

    Article  Google Scholar 

  • Jacobson-Kram D, Montalbano D (1985) The reproductive effects assessment group’s report on the mutagenicity of inorganic arsenic. Environ Mutagen 7: 787–804

    Article  Google Scholar 

  • Japanese Bioassay Research Center (1998) Summary data provided to BGVV by the Vinyl Acetate Toxicology Group, Inc.; in correspondence dated 2 December, 1998

    Google Scholar 

  • Jha AN, Noditi M, Nilsson R, Natarajan AT (1992) Genotoxic effects of sodium arsenite on human cells. Mutat Res 284: 215–221

    Article  Google Scholar 

  • Johnson K, Gorzinski S, Bodner K (1986) Chronic toxicity and oncogenicity study on acrylamide incorporated in the drinking water of Fischer 344 rats. Toxicol Appl Pharmacol 85: 154–168

    Article  Google Scholar 

  • Jones KG, Sweeney GD (1980) Dependence of the porphyrogenic effect of 2,3,7,8-tetra-chlorodibenzo-p-dioxin upon inheritance of aryl hydrocarbon hydroxylase responsiveness. Toxicol Appl Pharmacol 53: 42

    Article  Google Scholar 

  • Jones RW, Smith DM, Thomas PG (1988) A mortality study of vinyl chloride monomer workers employed in the United Kingdom in 1940–1974. Scand J Work Environ Health 14: 153–160

    Article  Google Scholar 

  • K.S.Crump Group Inc. (1999a) Consideration of the potency classification of acrylamide based on the incidence of tunica vaginalis mesotheliomas (TVMs) in male Fischer 344 rats. Prepared for the Acrylamide Monomer Producers Association (AMPA) Karlstr. 21, D-69200 Frankfurt/M

    Google Scholar 

  • K.S.Crump Group Inc. (1999b) Medchanism of acrylamide induction of benign fibroadenomas in the aging female Fischer 344 rat: Relevance to human health risk assessment. Prepared for the Acrylamide Monomer Producers Association (AMPA) Karlstr. 21, D-69200 Frankfurt/M

    Google Scholar 

  • Kadlubar FF, Kaderlik KR, Butler MA, Lin DX, Mulder GJ, Minchin RFM, Friesen MD, Bartsch H, Nago M, Esumi H, Sugimura T, Lang NP (1995) Metabolic activation of PhIP in rats, dogs, and humans. Princess Takamatsu Symp 1995 23: 207–213

    Google Scholar 

  • Kerckaert GA, LeBoeuf RA, Isofort RJ (1996) pH effects on the lifespan and transformation frequency of Syrian hamster embryo (SHE) cells. Carcinogenesis 17: 1819–1824

    Article  Google Scholar 

  • Kerns WD, Pavkov KL, Donofio DJ, Gralla EJ, Swenberg JA (1983) Carcinogenicity of formaldehyde in rats and mice after long-term inhalation exposure. Cancer Res 43: 4382–4392

    Google Scholar 

  • Kessler W, Remmer H (1990) Generation of volatile hydrocarbons from amino acids and proteins by an iron/ascorbate/GSH system. Biochem Pharmacol 39: 1347–1351

    Article  Google Scholar 

  • Kewitz H (1971) Nebenwirkungen contraceptiver Steroide. Westkreuz-Verlag, Berlin

    Google Scholar 

  • Kielhorn J, Melber C, Wahnschaffe U, Aitio A, Mangelsdorf I (2000) Vinyl chloride: still a cause for concern. Environ Health Perspect 108: 579–588

    Article  Google Scholar 

  • Kirkland DJ, Müller L (2000) Interpretation of the biological relevance of genotoxicity test results: the importance of thresholds. Mutat Res 464: 137–147

    Article  Google Scholar 

  • Kirman CR, Hays SM, Kedderis GL, Gargas ML, Strother DE (2000) Improving cancer dose-response characterization by using physiologically based pharmacokinetic modelling: an analysis of pooled data for acrylonitrile-induced brain tumours to assess cancer potency in the rat. Risk Anal 20: 135–150

    Article  Google Scholar 

  • Kirsch-Volders M, Aardema M, Elhajounji A (2000) Concepts of threshold in mutagenesis and carcinogenesis. Mutat Res 464: 3–11

    Article  Google Scholar 

  • Kitchin KT, Brown JL, Setzer RW (1994) Dose-response relationship in multistage carcinogenesis: promoters. Environ Health Perspect 102: 255–64

    Article  Google Scholar 

  • Kociba RJ (1991) Rodent bioassays for assessing chronic toxicity and carcinogenic potential of TCDD. In: Gallo MA, Scheuplein RJ, Van der Heijden K (eds) Biological Bbasis for risk assessment of dioxins and related compounds. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp 3–11

    Google Scholar 

  • Kociba RJ, Keyes DG, Beyer JE, Carreon RM, Wade CE, Dittenber DA, Kalnins RP, Frauson LE, Park CN, Barnard SD, Hummel RA, Humiston CG (1978) Results of a two-year chronic toxicity and oncogenicity study of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats. Toxicol Appl Pharmacol 46: 279–303

    Article  Google Scholar 

  • Kozak KR, Abbott B, Hankinson O (1997) ARNT-deficient mice and placental differentiation. Dev Biol 191: 287–305

    Article  Google Scholar 

  • Kozielski F, Arnal I, Wade RH (1998) A model of the microtubule-kinesin complex based on electron cryomicroscopy and X-ray crystallography. Curr Biol 8: 191–198

    Article  Google Scholar 

  • Kozielski F, Sack S, Marx A, Thormahlen M, Schonbrunn E, Biou V, Thompson A, Mandelkow EM, Mandelkow E (1997) The crystal structure of dimeric kinesin and implications for micro-tubule-dependent motility. Cell 91: 985–994

    Article  Google Scholar 

  • Kreiger RA, Garry VF (1983) Formaldehyde-induced cytotoxicity and sister-chromatid exchanges in human lymphocyte cultures. Mutat Res 120: 51–55

    Article  Google Scholar 

  • Kunz HW, Tennekes HA, Port RE, Schwarz M, Lorke D, Schaude G (1983) Quantitative aspects of chemical carcinogenesis and tumour promotion in liver. Environ Health Perspect 50: 113–122

    Article  Google Scholar 

  • Kuykendall JR, Bogdanffy MS (1992a) Reaction kinetics of DNA-histone crosslinking by vinyl acetate and acetaldehyde. Carcinogenesis 13: 2095–2100

    Article  Google Scholar 

  • Kuykendall JR, Bogdanffy MS (1992b) Efficiency of DNA-crosslinking induced by saturated and unsaturated aldehydes in vitro. Mutat Res 283: 131–36

    Article  Google Scholar 

  • Kuykendall JR, Bogdanffy MS (1994) Formation and stability of acetaldehyde-induced crosslinks between poly-lysine and poly-deoxyguanosine. Mutat Res 311: 49–56

    Article  Google Scholar 

  • Kuykendall JR, Taylor ML, Bogdanffy MS (1993) Cytotoxicity and DNA-protein crosslink formation in rat nasal tissues exposed vinyl acetate are carboxylesterase-mediated. Toxicol Appl Pharmacol 123: 283–292

    Article  Google Scholar 

  • Laib RJ, Bolt HM (1980) Trans-membrane-alkylation. A new method for studying irreversible binding of reactive metabolites to nucleic acids. Biochem Pharmacol 29: 449–452

    Google Scholar 

  • Laib RJ, Bolt HM (1986) Vinyl acetate, a structural analog of vinyl carbamate, fails to induce enzyme-altered foci in rat liver. Carcinogenesis 7: 841–843

    Article  Google Scholar 

  • Laib RJ, Pellio T, Wünschel UM, Zimmermann N, Bolt HM (1985) The rat liver foci bioassay: II. Investigations on the dose-dependent induction of ATPase-deficient foci by vinyl chloride at very low doses. Carcinogenesis 6: 69–72

    Article  Google Scholar 

  • Lam CW, Casanova M, Heck HDA (1985) Depletion of nasal mucosal glutathione by acrolein and enhancement of formaldehyde-induced DNA-protein cross-linking by simultaneous exposure to acrolein. Arch Toxicol 58: 67–71

    Article  Google Scholar 

  • Landrigan PJ (1999) Risk assessment for children and other sensitive populations. Ann NY Acad Sci 895: 1–9

    Article  Google Scholar 

  • Lang NP, Butler MA, Massengill J, Lawson M, Stotts RC, Hauer-Jensen M, Kadlubar FF (1994) Rapid metabolic phenotypes for acetyltransferase and cytochrome P4501A2 and putative exposure to food-borne heterocyclic amines increase the risk for colorectal cancer or polyps. Cancer Epidemiol Biomarkers Prev 3: 675–682

    Google Scholar 

  • Langouet S, Coles B, Morel F, Becquemont L, Beaune P, Guengerich FP, Ketterer B, Guillouzo A (1995) Inhibition of CYP1A2 and CYP3A4 by oltipraz results in reduction of aflatoxin Bl metabolism in human hepatocytes in primary culture. Cancer Res 55: 5574–5579

    Google Scholar 

  • Lawrence GS, Gobas FA (1997) A pharmacokinetic analysis of interspecies extrapolation in dioxin risk assessment. Chemosphere, 35: 427–452

    Article  Google Scholar 

  • LeBoeuf RA, Lin P, Kerchaert G, Gruenstein E (1992) Intracellular acidification is associated with enhanced morphological transformation in Syrian hamster embryo cells. Cancer Res 32: 144–148

    Google Scholar 

  • Lee TC, Tanaka N, Lamb PW, Gilmer TM, Barrett JC (1988) Induction of gene amplification by arsenic. Science 241: 79–81

    Article  Google Scholar 

  • Lee-Chen SF, Gurr JR, Lin IB, and Jan, KY (1993) Arsenite enhances DNA double-strand breaks and cell killing of methyl methanesulfonate-treated cells by inhibiting the excision of alkali-labile sites. Mutat Res 294: 21–28

    Article  Google Scholar 

  • Lehninger AL, Nelson DL, Cox MM (1993) Principles of biochemistry. Worth Publishers, New York, pp 506–541

    Google Scholar 

  • Leone G, Voso MT, Sica S, Morosetti R, Pagano L (2001) Therapy related leukemias: susceptibility, prevention and treatment. Leuk Lymphoma 41: 255–276

    Article  Google Scholar 

  • Leutner C, Schild H (2001) MRI of the lung parenchyma. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 173(3): 168–175

    Article  Google Scholar 

  • Lewis JL, Nikula KJ, Novak R, Dahl AR (1994) Comparative localization of carboxylesterase in F344 rat, beagle dog, and human nasal mucosa. Anat Rec 239: 55–64

    Article  Google Scholar 

  • Lieberman M, Kunishi AT, Mapson LW, Wardale DA (1965) Ethylene production from methionine. Biochem J 97: 449–459

    Google Scholar 

  • Lieberman M, Mapson LW (1964) Genesis and biogenesis of ethylene. Nature 204: 343–345

    Article  Google Scholar 

  • Lijinksy W, Reuber MD (1983) Chronic toxicity studies of vinyl acetate in Fischer rats. Toxicol Appl Pharmacol 68: 43–53

    Article  Google Scholar 

  • Lin DX, Lang NP, Kadlubar FF (1995) Species differences in the biotransformation of the food-borne carcinogen 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine by hepatic microsomes and cytosols from humans, rats, and mice. Drug Metab Dispos 23: 518–524

    Google Scholar 

  • Lotlikar PD, Jhee EC, Insetta SM, Clearfield MS (1984) Modulation of microsome-mediated aflatoxin B1 binding to exogenous and endogenous DNA by cytosolic glutathione S-transferase in rat liver. Carcinogenesis 5: 269–276

    Article  Google Scholar 

  • Lucier GW, Tritscher A, Goldsworthy T, Foley J, Clark G, Goldstein J, Maronpot R (1991) Ovarian hormones enhance 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated increases in cell proliferation and preneoplastic foci in a two-stage model for rat hepatocarcinogenesis. Cancer Res 51: 1391–1397

    Google Scholar 

  • Lutz U, Lugli S, Bitsch A, Schlatter J, Lutz WK (1997) Dose-responseDose-response for the stimulation of cell division by caffeic acid in forestomach and kidney of the male F344 rat, Fund Appl Toxicol 39: 131–237

    Article  Google Scholar 

  • Lutz WK (1986) Quantitative evaluation of DNA binding data for risk estimation and for classification of direct and indirect carcinogens. J Cancer Res Clin Oncol 112: 85–91

    Article  Google Scholar 

  • Lutz WK (1998) Dose-response relationships in chemical carcinogenesis: superposition of different mechanisms of action, resulting in linear-nonlinear curves, practical thresholds, J-shapes. Mutat Res 405: 117–124

    Article  Google Scholar 

  • Lutz WK (2000) A true threshold dose in chemical carcinogenesis cannot be defined for a population, irrespective of the mode of action. Hum Exp Toxicol 19: 566–68

    Article  Google Scholar 

  • Lutz WK (2001) Susceptibility differences in chemical carcinogenesis linearize the dose-response relationship: threshold doses can be defined only for individuals. Mutat Res 482: 71–76

    Article  Google Scholar 

  • Lutz WK, Jaggi W, Luthy J, Sagelsdorff P, Schlatter C (1980) In vivo covalent binding of aflatoxin B1 and aflatoxin M1 to liver DNA of rat, mouse and pig. Chem Biol Interact 32: 249–250

    Article  Google Scholar 

  • Lutz WK, Kopp-Schneider A (1999) Threshold dose-response for tumour induction by genotoxic carcinogens modelled via cell-cycle delay. Toxicol Sci 49: 110–115

    Article  Google Scholar 

  • Ma TH, Harris MM (1988) Review of the genotoxicity of formaldehyde. Mutat Res 196: 37–59

    Article  Google Scholar 

  • Maltoni C (1977) Recent findings on the carcinogenicity of chlorinated olefins, Environ Health Perspect 21: 1–5

    Article  Google Scholar 

  • Maltoni C, Ciliberti A, Lefemine G, Soffritti M (1997) Results of a long-term experimental study on the carcinogenicity of vinyl acetate monomer in mice. Ann NY Acad Sci 209–238

    Google Scholar 

  • Maltoni C, Lefemine C, Chieco P, Carretta D (1974) Vinyl chloride carcinogenesis. Current results and perspectives. Med Lav 65: 421

    Google Scholar 

  • Maltoni C, Lefemine G, Ciliberti A, Cotti G, Carretti D (1981) Carcinogenicity bioassay of vinyl chloride monomer: a model of risk assessment on an experimental basis. Environ Health Per-spect 41:2–29

    Google Scholar 

  • Maltoni C, Lefemine G, Ciliberti A, Cotti G, Carretti D (1984) Experimental research on vinyl chloride carcinogenesis. In: Maltoni C, Mehlman M (eds) Archives of Research on Industrial Carcinogenesis, Vol. 2. Princeton Scientific Publishers., Princeton, NJ

    Google Scholar 

  • Manz A, Berger J, Dwyer JH, Flesch-Janys D, Nagel S, Waltsgott H (1991) Cancer mortality among workers in chemical plant contaminated with dioxin. Lancet 338: 959–64

    Article  Google Scholar 

  • McConnell EE, Solleveld HA, Swenberg JA, Boorman GA (1986) Guidelines for combining neoplasms for evaluation of rodent carcinogenesis studies. J Natl Cancer Inst 76: 283–289

    Google Scholar 

  • McDonald TA, Holland NT, Skibola C, Duramad P, Smith MT (2001) Hypothesis: phenol and hydroquinone derived mainly from diet and gastrointestinal flora activity are causal factors in leukemia. Leukemia 15: 10–20

    Article  Google Scholar 

  • McMahon G, Davis EF, Huber LJ, Kim Y, Wogan GN (1990) Characterization of c-Ki-ras and N-ras oncogenes in aflatoxinaflatoxin B1-induced rat liver tumours. Proc Natl Acad Sci USA 8: 1104–1108

    Article  Google Scholar 

  • Monticello TM, Swenberg JA, Gross EA, Leininger JR, Kimbell JS, Seilkop S, Starr TB, Gibson JE, Morgan KT (1996) Correlation of regional and nonlinear formaldehyde-induced nasal cancer with proliferating populations of cells. Cancer Res 56: 1012–1022

    Google Scholar 

  • Moolgavkar SH, Luebeck EG (1990) Two event model for carcinogenesis: biological, mathematical and statistical considerations. Risk Anal 10: 323–341

    Article  Google Scholar 

  • Moolgavkar SH, Luebeck EG, Krewski D, Zieliski JM (1993) Radon, cigarette smoke, and lung cancer: a reanalysis of the Colorado uranium miners’ data.. Am J Epidemiol 4: 207–217

    Google Scholar 

  • Moore MM, Harrington-Brock K, Doerr CL (1997) Relative genotoxic potency of arsenic and its methylated metabolites. Mutat Res 386(3):279–290

    Article  Google Scholar 

  • Morel F, Fardel O, Meyer DJ, Langouet S, Gilmore KS, Meunier B, Tu CP, Kensler TW, Ketterer B, Guillouzo A (1993) Preferential increase of glutathione S-transferase class alpha transcripts in cultured human hepatocytes by phenobarbital, 3-methylcholanthrene, and dithiolethiones. Cancer Res 53: 231–234

    Google Scholar 

  • Morel F, Langouet S, Maheo K, Guillouzo A (1997) The use of primary hepatocyte cultures for the evaluation of chemoprotective agents. Cell Biol Toxicol 13: 323–329

    Article  Google Scholar 

  • Morgan KT (1997) A brief review of formaldehyde carcinogenesis in relation to rat nasal pathology and human risk assessment. Toxicol Pathol 25: 291–307

    Article  Google Scholar 

  • Morgan KT, Jiang XZ, Starr TB, Kerns WD (1986) More precise localization of nasal tumours associated with chronic exposure of F344 rats to formaldehyde gas. Toxicol Appl Pharmacol 82:264–271

    Article  Google Scholar 

  • Morita T (1995) Low pH leads to sister-chromatid exchanges and chromosomal aberrations, and its clastogenicity is S-dependent. Mutat Res. 334: 301–308

    Article  Google Scholar 

  • Moritz H (1989) Investigation of tumor initiating and/or cocarcinogenic properties of arsenite and arsenate with the rat liver foci bioassay. Exp Pathol 37: 231–233

    Article  Google Scholar 

  • Nair J, Barbin A, Guichard Y, Bartsch H (1995) 1,N 6-Ethenodeoxyadenosine and 3,N 4-ethen-odeoxycytidine in liver DNA from humans and untreated rodents detected by immunoafdfini-try/32P-postlabelling. Carcinogenesis 16: 613–617

    Article  Google Scholar 

  • Nakai JS, Winhall MJ, Bunce NJ (1994) Comparative kinetic study of the binding between 2,3,7,8-tetrachlorodibenzo-p-dioxin and related ligands with the hepatic Ah receptors from several rodent species. J Biochem Toxicol 9: 199–209

    Article  Google Scholar 

  • Nath RG, Randerath K, Donghui L, Chung FL (1996) Endogenous production of DNA adducts. Regulat Toxicol Pharmacol 23:22–28

    Article  Google Scholar 

  • Nedergaard M, Goldman SA, Desai S, Pulsinelli WA (1991) Acid-induced death in neurons and glia. JNeurosci 11: 2489–2497

    Google Scholar 

  • Nelson LW, Weikel JH, Reno FE (1973) Mammary nodules in dogs during four years’ treatment with megestrol acetate or Chlormadinone acetate. J Natl Cancer Inst 51: 1303

    Google Scholar 

  • Neumann F, Elger W (1971) Kritische Überlegungen zu den biologischen Grundlagen von Toxiz-itätsstudien mit Sexualhormonen. In: Plotz EJ, Haller J (eds) Methodik der Steroidtoxikologie, Thieme, Stuttgart, p 7

    Google Scholar 

  • Neumann HG, Vamvakas S, Thielmann HW, Gelbke HP, Filser JG, Reuter U, Greim H, Kappus H, Norpoth KH, Wardenbach P, Wichmann HE (1998) Changes in the classification of carcinogenic chemicals in the work area. Int Arch Occup Environ Health 71: 566–574

    Article  Google Scholar 

  • Obe G, Natarajan AT, Meyers M, Den Hertog A (1979) Induction of chromosomal aberrations in peripheral lymphocytes of human blood in vitro, and of SCEs in bone-marrow cells of mice in vivo by ethanol and its metabolite acetaldehyde. Mutat Res 68: 291–294

    Article  Google Scholar 

  • Oesch F, Arand M, Hengstler JG (2000) Enzympolymorphismen als Ursachen erhöhter Suszepti-bilität in der chemischen Karzinogenese. In: Müller WU, Heinemann G, Fehringer F (eds) Strahlenbiologie und Strahlenschutz, individuelle Strahlenempfindlichkeit und Strahlenschutz. Publikationsreihe: Fortschritte im Strahlenschutz, Band II, Bad Kissingen, pp 374–393

    Google Scholar 

  • Oesch F, Hengstler JG, Fuchs J (1994) Cigarette smoking protects mononuclear blood cells of carcinogen exposed workers from additional work-exposure induced DNA single strand breaks. Mutat Res 321: 175–185

    Article  Google Scholar 

  • Oesch F, Herrero ME, Hengstler JG, Lohmann M, Arand M (2000) Metabolic detoxification: implications for thresholds. Toxicol Pathol 28: 382–87

    Article  Google Scholar 

  • Oganesian A, Hendricks JD, Pereira CB, Orner GA, Bailey GS, Williams DE (1999) Potency of dietary indole-3-carbinol as a promoter of Aflatoxin B1-initiated hepatocarcinogenesis: results from a 9000 animal tumour study. Carcinogenesis 20: 453–58

    Article  Google Scholar 

  • Ohmori S, Horie T, Guengerich FP, Kiuchi M, Kitada M (1993) Purification and characterization of two forms of hepatic microsomal cytochrome P450 from untreated Cynomolgus monkeys. Arch Biochem Biophys 305: 405–413

    Article  Google Scholar 

  • Olson JR, Holscher MA, Neal RA (1980) Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the golden Syrian hamster. Toxicol Appl Pharmacol 55: 67–78

    Article  Google Scholar 

  • Olson MJ, Martin JL, Larosa AC, Brady AN, Pohl LR (1993) Immunohistochemical localization of carboxylesterase in the nasal mucosa of rats. J Histochem Cytochem 41: 307–311

    Article  Google Scholar 

  • Organisation for Economic Co-operation and Development [OECD] (1981) Combined chronic toxicity/carcinogenicity studies. Test Nr. 453.OECD Guidelines for Testings of Chemicals. OECD, Paris

    Google Scholar 

  • Organisation for Economic Co-operation and Development [OECD] (1998) Repeated dose 90-day oral toxicity study in rodents. Test Nr. 408. OECD Guidelines for Testings of Chemicals. OECD, Paris

    Google Scholar 

  • Östergaard G, Knudsen I (1998) The applicability of the ADI (Acceptable Daily Intake) for food additives to infants and children. Food Addit Contam 15, Suppl: 63–74

    Google Scholar 

  • Ott MG, Teta MJ, Greenberg HL (1989) Lymphatic and hematopoietic tissue cancer in a chemical manufacturing environment. Am J Ind Med 16: 631–643

    Google Scholar 

  • Park J, Kamendulis LM, Friedman MA, Klaunig JE (2002) Acrylamide-induced cellular transformation. Toxicol Sci 65: 177–183

    Article  Google Scholar 

  • Parry JM (2000) Reflections on the implications of thresholds of mutagenic activity for the labelling of chemicals by the European Union. Mutat Res 464: 155–158

    Article  Google Scholar 

  • Parry JM, Jenkins GJS, Haddad F, Bourner R, Parry EM (2000) In vitro and in vivo extrapolations of genotoxin exposures: consideration of factors which influence dose-response thresholds. Mutat Res 464: 53–63

    Article  Google Scholar 

  • Peers FG, Linsell CA (1977) Dietary aflatoxins and human primary liver cancer. Ann Nutr Aliment 31: 1005–1018

    Google Scholar 

  • Pellizzari ED (1982) Analysis for organic vapor emissions near industrial and chemical waste disposal sites. Environ Sci Technol 16: 781–85

    Article  Google Scholar 

  • Pershagen G, Lind B, Björklund NE (1982) Lung retention and toxicity of some inorganic arsenic compounds. Environ Res 29: 425–434

    Article  Google Scholar 

  • Pershagen G, Norberg G, Björklund NE (1984) Carcinomas of the respiratory tract in hamsters given arsenic trioxide and/or benxo(a)pyrene by the pulmonary route. Environ Res 34: 227–241

    Article  Google Scholar 

  • Peter H, Wiegand HJ, Bolt HM, Greim H, Walter G, Berg M, Filser JG (1987) Pharmacokinetics of isoprene in mice and rats. Toxicol Lett 36: 9–14

    Article  Google Scholar 

  • Peterson RE, Theobal HM, Kimmel GL (1993) Developmental and reproductive toxicity of dioxins and related compounds: cross-species comparisons. Crit Rev Toxicol 23: 283–335

    Article  Google Scholar 

  • Peto R, Gray R, Brantom P, Grasso P (1991) Effects on 4080 rats of chronic ingestion of N-nitrosodi-ethylamine or N-nitrosodimethylamine: a detailed dose-response study. Cancer Res 51: 6415–6451

    Google Scholar 

  • Placke ME, Griffis L, Bird M, Bus M, Persing RL, Cox LA (1996) Chronic inhalation oncogenicity study of isoprene in B6C3F1 mice. Toxicology 110: 253–262

    Article  Google Scholar 

  • Plowchalk DR, Andersen ME, Bogdanffy MS (1997) Physiologically based modelling of vinyl acetate uptake, metabolism, and intracellular pH changes in the rat nasal cavity. Toxicol Appl Pharmacol 142: 386–400

    Article  Google Scholar 

  • Pohjanvirta R, Viluksela M, Tuomisto JT, Unkila M, Karasinska J, Franc MA, Holowenko M, Giannone JV, Harper PA, Tuomisto J, Okey AB (1999) Physicochemical differences in the AH receptors of the most TCDD-susceptible and the most TCDD-resistant rat strains. Toxicol Appl Pharmacol 155: 82–95

    Article  Google Scholar 

  • Poirier MC, Beland FA (1992) DNA adduct measurements and tumour incidence during chronic carcinogen exposure in animal models: implications for DNA adduct-based human cancer risk assessment. Chem Res Toxicol 5: 749–755

    Article  Google Scholar 

  • Poirier MC, Fullerton NF, Smith BA, Beland FA (1995) DNA adduct formation and tumourigene-sis in mice during the chronic administration of 4-aminobiphenyl at multiple dose levels. Carcinogenesis 16:2917–2921

    Article  Google Scholar 

  • Poland A, Glover E (1980) 2,3,7,8-tetrachlorodibenzo-/?-dioxin: segregation of toxicity with the Ah locus. Mol Pharmacol 17: 86

    Google Scholar 

  • Poland A, Palen D, Glover E (1994) Analysis of the four alleles of the murine aryl hydrocarbon receptor. Mol Pharmacol 46: 915–921

    Google Scholar 

  • Poma K, Degraeve N, Susanne C (1987) Cytogenic effects in mice after chronic exposure to arsenic followed by a single dose of ethyl methanesulfonate. Cytologia 52: 445–450

    Article  Google Scholar 

  • Portier C, Hoel D, van Ryzin J (1984) Statistical analysis of the carcinogenesis bioassay data relating to the risks from exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. In: Lowrance WW (ed) Public health risks of the dioxins. W Kaufmann, Los Altos, NM, pp 99–120

    Google Scholar 

  • Preston-Marin S, Pike MC, Ross RK, Jones PA, Henderson RE (1990) Increased cell division as a cause of human cancer. Cancer Res 50: 7415–7421

    Google Scholar 

  • Quinn BA, Crane TL, Kocal TE, Best S J, Cameron RG, Rushmore TH, Faber E, Haye MA (1990) Protective activity of different hepatic cytosolic glutathione S-transferases against DNA-binding metabolites of aflatoxin B1 Toxicol Appl Pharmacol 105: 351–363

    Google Scholar 

  • Ramsdell HS, Eaton DL (1990) Species susceptibility to aflatoxin B1 carcinogenesis: comparative kinetics of microsomal biotransformation. Cancer Res 50: 615–620

    Google Scholar 

  • Randerath K, Putnam KL, Osterburg HH, Johnson SA, Morgan DG, Finch CE (1993) Age-dependent increase of DNA adducts (I-compounds) in human and rat brain DNA. Mutat Res 295:11–18

    Article  Google Scholar 

  • Rasmussen BB, Brosen K (1996) Determination of urinary metabolites of caffeine for the assessment of cytochrome P450 1A2, xanthine oxidase, and N-acetyltransferase activity in humans. Ther Drug Monit 18: 254–262

    Article  Google Scholar 

  • Ray S, Meyhöfer E, Milligan RA, Howard J (1993) Kinesin follows the microtubule’s protofila-ment axis. J Cell Biol 121: 1083–1093

    Article  Google Scholar 

  • Record IR, Broadbent JL, King RA, Dreosti IE, Head RJ, Tonkin AL (1997) Genistein inhibits growth of B16 melanoma cells in vivo and in vitro and promotes differentiation in vitro. Int J Cancer 72: 860–864

    Article  Google Scholar 

  • Reed CJ, Robinson DA (1998) Histochemical localisation and biochemical quantitation of car-boxylesterase activity in rat and mouse oral cavity mucosa. Report to the Vinyl Acetate Toxicology Group, School of Biomolecular Sciences, John Moores University, Liverpool

    Google Scholar 

  • Reese JS, Allay E, Gerson SL (2001) Overexpression of human O 6-alkylguanine DNA alkyltrans-ferase (AGT) prevents MNU induced lymphomas in heterozygous p53 deficient mice. Oncogene 20: 5258–5263

    Article  Google Scholar 

  • Reitz RH, Gargas ML, Andersen ME, Provan WM, Green TL (1996) Predicting cancer risk from vinyl chloride exposure with a physiologically based pharmacokinetic model. Toxicol Appl Pharmacol 137: 253–267

    Article  Google Scholar 

  • Renwick AG, Dorne JL, Walton K (2000) An analysis of the need for an additional uncertainty factor for infants and children. Regul Toxicol Pharmacol 31: 286–296

    Article  Google Scholar 

  • Roberts-Thomson IC, Ryan P, Khoo KK, Hart WJ, McMichael AJ, Butler RN (1996) Diet, acety-lator phenotype, and risk of colorectal neoplasia. Lancet 347: 1372–1374

    Article  Google Scholar 

  • Ross JA (1998) Maternal diet and infant leukemia: a role for DNA topoisomerase II inhibitors? Int J Cancer Suppl 11:26–28

    Article  Google Scholar 

  • Ross JA (2000) Dietary flavonoids and the MLL gene: a pathway to infant leukemia? Proc Natl Acad Sci USA 97: 4411–4413

    Article  Google Scholar 

  • Ross WE, McMillan DR, Ross CF (1981) Comparison of DNA damage by methylmelanines and formaldehyde. J Natl Cancer Inst 67: 217–221

    Google Scholar 

  • Ross WE, Shipley N (1980) Relationship between DNA damage and survival in formaldehyde-treated mouse cells. Mutat Res 79: 277–283

    Article  Google Scholar 

  • Rotstein JB, Slaga TJ (1988) Acetic acid, a potent agent of tumour progression in the multistage mouse skin model for chemical carcinogenesis. Cancer Lett 42: 87–90

    Article  Google Scholar 

  • Rozman K (1989) A critical review on the mechanisms of toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Implications for human safety assessment. Derm Beruf Umwelt 38: 95–95

    Google Scholar 

  • Sadrieh N, Snyderwine EG (1995) Cytochromes P450 in cynomolgus monkeys mutagenically activate 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) but not 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx). Carcinogenesis 16: 1549–1555

    Article  Google Scholar 

  • Sagai M, Ichinose T (1980) Age-related changes in lipid peroxidation as measured by ethane, ethylene, butane and pentane in respired gases in rats. Life Sci 27: 731–738

    Article  Google Scholar 

  • Sarangapani R, Teeguarden J, Clewell HJ, Centry R, Covington T, Andersen ME (2000) Oral hazard identification and dose-response characterization for vinyl acetate. Report to the Vinyl Acetate Toxicology Group, KS Crump Group, ICF Consulting, Research Triangle Park, NC

    Google Scholar 

  • Schieferstein GJ, Littlefield NA, Gaylor DW, Sheldon WG, Burger GT (1985) Carcinogenesis of 4-aminobiphenyl in BALB/cStCrlfC3Hf/Nctr mice. Eur J Cancer Clin Oncol 21: 865–873

    Article  Google Scholar 

  • Schiffmann MH, Felton JS (1990) Fried foods and the risk of colon cancer. Am J Epidemiol 131: 376–378

    Google Scholar 

  • Schoeny R (1996) Use of genetic toxicology data in US EPA risk assessment: the mercury study report as an example. Environ Health Perspect 104, Suppl. 3: 663–673

    Google Scholar 

  • Schrenk D, Stuven T, Goh G, Viebahn R, Bock KW (1995) Induction of CYP1A and glutathione S-transferase activities by 2,3,7,8-tetrachlorodibenzo-p-dioxin in human hepatocyte cultures. Carcinogenesis 16: 943–946

    Article  Google Scholar 

  • Schroder-van der Elst JP, van der Heide D, Rokos H, Morreale de Escobar G, Kohrle J (1998) Synthetic flavonoids cross the placenta in the rat and are found in fetal brain. Am J Physiol 274: 253–256

    Google Scholar 

  • Schulte-Hermann R, Bursch W, Kraupp-Grasl B, Oberhammer F, Wagner A (1992) Programmed cell death and its protective role with particular reference to apoptosis. Toxicol Lett 64–65: 569–574

    Article  Google Scholar 

  • Schumann AM, Watanabe PG, Reitz RH, Gehring PJ (1982) The importance of pharmacokinetic and macromolecular events as they relate to mechanisms of tumourigenicity and risk assessment. In: Plaa G, Hewitt WR (eds) Toxicology of the Liver. Target Organ Toxicology Series, Raven Press, New York, pp 311–331

    Google Scholar 

  • Schwenk M, Gundert-Remy U, Heinemeyer G, Olejniczak K, Stahlmann R, Kaufmann W, Bolt HM, Greim H, von Keutz E, Gelbke HP (2003) Children as a sensitive subgroup and their role in regulatory toxicology. Arch Toxicol 77: 2–6

    Article  Google Scholar 

  • Schwetz B, Norris J, Sparschu G, Rowe V, Gehring P, Emerson J, Gerbig C (1973) Toxicology of chlorinated dibenzo-p-dioxins. Environ Health Perspect 5: 87–99

    Article  Google Scholar 

  • Scott WJ, Beliles RP, Silverman HI (1971) The comparative acute toxicity of two cardiac glycosides in adult and newborn rats. Toxicol Appl Pharmacol 20: 599–601

    Article  Google Scholar 

  • Seeley MR, Tonner-Navarro, LE, Beck, BD, Deskin R, Feron VJ, Johanson G, Bolt HM (2001) Procedures of health risk assessment in Europe. Regul Toxicol Pharmacol 34: 153–169

    Article  Google Scholar 

  • Sellakumar AR, Snyder CA, Solomon JJ, Albert RE (1985) Carcinogenicity of formaldehyde and hydrogen chloride in rats. Toxicol Appl Pharmacol 81: 401–106

    Article  Google Scholar 

  • Sesardic D, Boobis AR, Edwards RJ, Davies DS (1989) A form of cytochrome P450 in man, orthologous to form d in the rat catalyzes the O-deethylation of phenacetin and is inducible by cigarette smoking. Br J Clin Pharmacol 26: 363–372

    Article  Google Scholar 

  • Sesardic D, Cole KJ, Edwards RJ, Davies DS, Thomas PE, Levin W, Boobis AR (1990) The inducibility and catalytic activity of cytochromes P450c (P4501A1) and P450d (P4501A2) in rat tissues. Biochem Pharmacol 39: 499–506

    Article  Google Scholar 

  • Shank RC, Bhamarapravati N, Gordon JE, Wogan GN (1972) Dietary aflatoxins and human liver cancer. IV Incidence of primary liver cancer in two municipal populations in Thailand. Food Cosmet Toxicol 10: 171–179

    Article  Google Scholar 

  • Shelanski ML, Gaskin F, Cantor CR (1973) Microtubule assembly in the absence of added nucleotides. Proc Natl Acad Sci USA 70: 765–768

    Article  Google Scholar 

  • Shen J, Kessler W, Denk B, Filser JG (1989) Metabolism and endogenous production of ethylene in rat and man. Arch Toxicol Suppl 13: 237–239

    Article  Google Scholar 

  • Sickles DW, Brady ST, Testino A, Friedman MA, Wrenn RW (1996) Direct effect of the neurotoxicant acrylamide on kinesin-based microtubule motility. J Neurosci Res 46: 7–17

    Article  Google Scholar 

  • Simon P, Filser JG, Bolt HM (1985) Metabolism and pharmacokinetics of vinyl acetate. Arch Toxicol 57: 191–95

    Article  Google Scholar 

  • Simon P, Ottenwälder H, Bolt HM (1985) Vinyl acetate: DNA-binding assay in vivo. Toxicol Lett 27: 115–120

    Article  Google Scholar 

  • Simonato L, L’Abbe KA, Andersen A, Belli S, Comba P, Engholm G, Ferro G, Hagmar L, Langard S, Lundberg I (1991) A collaborative study of cancer incidence and mortality among vinyl chloride workers. Scand J Work Environ Health 17: 159–169

    Article  Google Scholar 

  • Sinha R, Rothman N, Brown ED, Mark SD, Hoover RN, Caporaso NE, Levander OA, Knize MG, Lang NP, Kadlubar FF (1994) Pan-fried meat containing high levels of heterocyclic aromatic amines but low levels of poly cyclic aromatic hydrocarbons induces cytochrome P450 1A2 activity in humans. Cancer Res 54: 6154–6159

    Google Scholar 

  • Sipi P, Joarventaus H, Norppa H (1992) Sister-chromatid exchanges induced by vinyl esters and respective carboxylic acids in cultured human lymphocytes. Mutat Res 279: 75–83

    Article  Google Scholar 

  • Slone DH, Gallagher EP, Ramsdell HS, Rettie AE, Stapleton PL, Berlad LG, Eaton DL (1995) Human variability in hepatic glutathione S-transferase-mediated conjugation of aflatoxin B1 epoxide and other chemicals. Pharmacogenetics 5: 224–233

    Article  Google Scholar 

  • Snyderwine EG, Turesky RJ, Turteltaub KW, Davis CD, Sadrieh N, Schut HA, Nagao M, Sugimura T, Thorgeirsson UP, Adamson RH, Thorgeirsson SS (1997) Metabolism of food-derived heterocyclic amines in nonhuman primates. Mutat Res 376: 203–210

    Article  Google Scholar 

  • Solleveld HA, Haseman JK, McConnell EE (1984) Natural history of body weight gain, survival and neoplasia in the F344 rat. J Natl Cancer Inst 72: 929–40

    Google Scholar 

  • Solomon MJ, Varshavsky A (1985) Formaldehyde-mediated DNA-protein crosslinking: A probe for in vivo chromatin structures. Proc Natl Acad Sci USA 82: 6470–6474

    Article  Google Scholar 

  • Soman NR, Wogan GN (1993) Activation of the c-Ki-ras oncogene in Aflatoxin B1-induced hepatocellular carcinoma and adenoma in the rat: detection by denaturing gradient gel electrophoresis. Proc Natl Acad Sci USA 90: 2045–2049

    Article  Google Scholar 

  • Sosa H, Hoenger A, Milligan RA (1997) Three different approaches for calculating the three-dimensional structure of microtubules decorated with kinesin motor domains. J Struct Biol 118: 149–158

    Article  Google Scholar 

  • Squire RA, Cameron LL (1984) An analysis of potential carcinogenic risk from formaldehyde. Regul Toxicol Pharmacol 4: 107–129

    Article  Google Scholar 

  • Staffa JA, Mehlman MA (1979) Innovations in cancer risk assessment (ED01 study). Environ Pathol Toxicol 3: 1–246

    Google Scholar 

  • Staretz ME, Foiles PG, Miglietta LM, Hecht SS (1997) Evidence for an important role of DNA pyridyloxobutylation in rat lung carcinogenesis by 4-(methylnitrosamino)-l-(3-pyridyl)-1-butanone: effects of dose and phenethyl isothiocyanate. Cancer Res 57: 259–266

    Google Scholar 

  • Starr TB, Buck RD (1984) The importance of delivered dose in estimating low-dose cancer risk from inhalation exposure to formaldehyde. Fund Appl Toxicol 4: 740–753

    Article  Google Scholar 

  • Steenland K, Deddens J, Piacitelli L (2001) Risk assessment for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) based on an epidemiologic study. Am J Epidemiol 154: 451–458

    Article  Google Scholar 

  • Steinberg P, Jennings GS, Schlemper B, Oesch F (1996) Molecular mechanisms underlying the liver cell-type specific toxicity of aflatoxin B1. In: Hengstler JG, Oesch F (eds) Control Mechanisms of Carcinogenesis, Druckerei Thieme, Mainz

    Google Scholar 

  • Steinmetz KL, Green CE, Bakke JP, Spak DK, Mirsalis JC (1988) Induction of unscheduled DNA synthesis in primary cultures of rat, mouse, hamster, and human hepatocytes. Mutat Res 206: 91–102

    Article  Google Scholar 

  • Stone R (1995) A molecular approach to cancer risk. Science 268: 356–357

    Article  Google Scholar 

  • Storm JE, Rozman ICK (1997) Evaluation of alternative methods for establishing safe levels of occupational exposure to vinyl halides. Regul Toxicol Pharmacol 25: 240–255

    Article  Google Scholar 

  • Stott WT, McKenna MJ (1985) Hydrolysis of several glycol ether acetates and acrylate esters by nasal mucosal carboxylesterase in vitro. Fundam Appl Toxicol 5: 399–404

    Article  Google Scholar 

  • Strick R, Strissel PL, Borgers S, Smith SL, Rowley JD (2000) Dietary bioflavonoids induce cleavage in the MLL gene and may contribute to infant leukemia. Proc Natl Acad Sci USA 97: 4790–4795

    Article  Google Scholar 

  • Swenberg JA, Barrow CS, Boreiko CD, Heck HDA, Levine RJ, Morgan KT, Starr TB (1983b) Non-linear biological responses to formaldehyde and their implications for carcinogenic risk assessment. Carcinogenesis 4: 945–952

    Article  Google Scholar 

  • Swenberg JA, Gross EA, Randall HW, Barrow CS (1983a) In: Clary JJ, Gibson JE, Waritz RS, (eds) Formaldehyde: toxicology, epidemiology, mechanisms. Marcel Dekker, New York, pp 225–236

    Google Scholar 

  • Swenberg JA, Ham A, Koc H, Morinello E, Ranasinghe A, Tretyakova N, Upton PB, Wu KY (2000) DNA adducts: effects of low exposure to ethylene oxide, vinyl chloride and butadiene. Mutat Res 464: 77–86

    Article  Google Scholar 

  • Swenberg JA, Kerns WD, Mitchell RE, Gralla EJ, Pavkov KL (1980) Induction of squameous cell carcinomas of the rat nasal cavity by inhalation exposure to formaldehyde vapor. Cancer Res 40: 3398–3402

    Google Scholar 

  • Swenson DH, Lin JK, Miller EC, Miller JA (1977) Aflatoxin Br2,3-oxide as a probable intermediate in the covalent binding of aflatoxins B1 and B2 to rat liver DNA and ribosomal RNA in vivo. Cancer Res 37: 172–81

    Google Scholar 

  • Tareke E, Rydberg P, Karlsson P, Eriksson S, Törnqvist M (2000) Acrylamide: a cooking carcinogen? Cherm Res Toxicol 13: 517–522

    Article  Google Scholar 

  • Teeguarden JG, Dragan YP, Singh J, Vaughan J, Xu YH, Goldsworthy T, Pitot HC (1999) Quantitative analysis of dose- and time-dependent promotion of four phenotypes of altered hepatic foci by 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Sprague-Dawley rats. Toxicol Sci 51: 211–23

    Article  Google Scholar 

  • Thier R, Bolt HM (2000) Carcinogenicity and genotoxicity of ethylene oxide: new aspects and recent advances. Crit Rev Toxicol 30: 595–608

    Article  Google Scholar 

  • Thier R, Bonacker D, Stoiber T, Böhm KJ, Wang M, Unger E, Bolt HM, Degen G (2003a) Interaction of metal salts with cytoskeletal motorprotein systems. Toxicol Lett 140/141: 75–81

    Article  Google Scholar 

  • Thier R, Brüning T, Roos PH, Rihs HP, Golka K, Ko Y, Bolt HM (2003b) Markers of genetic susceptibility in human environmental hygiene and toxicology: the role of selected CYP, NAT and GSTgenes. Int J Hyg Environ Health 206: 149–171

    Article  Google Scholar 

  • Tobey NA, Reddy SP, Keku TO, Cragoe EJ, Orlando RC 1992. Studies of pH, in rabbit esophageal basal and squamous epithelial cells in culture. Gastroenterology 103: 830–839

    Google Scholar 

  • Toonen TR, Hande KR (2001) Topoisomerase II inhibitors. Cancer Chemother Biol Response Modif 19: 129–147

    Google Scholar 

  • Törnqvist M, Almberg JG, Bergmark EN, Nilsson S, Osterman-Golkar S (1989a) Ethylene oxide doses in ethene-exposed fruit store workers. Scand J Work Environ Health 15: 436–438

    Article  Google Scholar 

  • Törnqvist M, Gustafsson B, Kautiainen A, Harms-Ringdahl M, Granath F, Ehrenberg L (1989b) Unsaturated lipids and intestinal bacteria as sources of endogenous production of ethene and ethylene oxide. Carcinogenesis 10: 39–41

    Article  Google Scholar 

  • Tseng WP (1977) Effects and dose-response relationships of skin cancer and Blackfoot disease with arsenic. Environ Health Perspect 19: 109–119

    Article  Google Scholar 

  • Tseng WP, Chu HM, How SW, Fong JM, Lin CS, Yen S (1968) Prevalence of skin cancer in an endemic area of chronic arsenicism in Taiwan. J Natl Cancer Inst USA 40: 453–463

    Google Scholar 

  • Tuomisto JT, Viluksela M, Pohjanvirta R, Tuomisto J (1999) The AH receptor and a novel gene determine acute toxic responses to TCDD: segregation of the resistant alleles to different rat lines (1999) Toxicol Appl Pharmacol 155: 71–81

    Google Scholar 

  • Turesky RJ, Aeschbacher HU, Würzner HP, Skipper PL, Tannenbaum SR (1988) Major routes of metabolism of the food-borne carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in the rat. Carcinogenesis: 9: 1043–1048

    Article  Google Scholar 

  • Ueno I, Friedman L, Stone CL (1980) Species difference in the binding of aflatoxin B1 to hepatic macromolecules. Toxicol Appl Pharmacol 52: 177–180

    Article  Google Scholar 

  • Unkila M, Pohjanvirta R, MacDonald E, Tuomistro J (1994) Characterization of 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD)-induced brain serotonin metabolism in the rat. Eur J Pharmacol 270: 157–166

    Google Scholar 

  • Unkila M, Ruotsalainen M, Pohjanvirta R, Viluksela M, MacDonald E, Tuomistro J, Rozman K, Tuomisto J (1995) Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on tryptophan and glucose homeostasis in most TCDD-susceptible and the most TCDD-resistent species, guinea pigs and hamsters. Arch Toxicol 69: 677–683

    Article  Google Scholar 

  • US Environmental Protection Agency [EPA] (1988) Special report on ingested inorganic arsenic: skin cancer; nutritional essentiality. EPA Report, EPA/625/3–87/013. Risk Assessment Forum, Washington, DC

    Google Scholar 

  • US Environmental Protection Agency [EPA] (1996) Proposed guidelines for carcinogen risk assessment. US Fed. Register 61, No.79, April 23, 1996. US Environmental Protection Agency, Washington, DC, available at http: //www.epa.gov./ORD/WebPubs/carcinogen/

    Google Scholar 

  • US Environmental Protection Agency [EPA] (2000) Vinyl chloride, IRIS file online, US Environmental Protection Agency, Washington, DC; available at http://www.epa.gov/iris/subst/1001.htm/

    Google Scholar 

  • US Environmental Protection Agency [EPA] (2003) Arsenic, inorganic (CASRN 7440–38–2) In: U.S. Environmental Protection Agency Integrated Risk Information System (IRIS) http://www.epa.gov/iris/subst/0278.htm

    Google Scholar 

  • Van Sittert NJ, Boogaard PJ, Natarajan AT, Tates AD, Ehrenberg LG, Törnqvist MA (2000) Formation of DNA adducts and induction of mutagenic effects in rats following 4 weeks inhalation exposure to ethylene oxide as a basis for cancer risk assessment. Mutat Res 447: 27–48

    Article  Google Scholar 

  • Vecchi A, Sironi M, Antonia M, Recchia CM, Garattini S (1983) Immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in strains of mice with different susceptibility. Proc Natl Acad Sci USA 87: 6917

    Google Scholar 

  • Vielhauer V, Sarafoff M, Gais P, Rabes HM (2001) Cell type-specific induction of O 6 -alkylgua-nine-DNA alkyltransferase mRNA expression in rat liver during regeneration, inflammation and preneoplasia. J Cancer Res Clin Oncol 127: 591–602

    Article  Google Scholar 

  • Von Mach MA (2002) Primary biliary cirrhosis in classmates: coincidence or enigmatic environmental influence? EXCLI Journal 1:1–7

    Google Scholar 

  • Von Mach MA, Lauterbach M, Kaes J, Hengstler JG, Weilemann JG (2003) Suizidale und parasuizidale Intoxikationen mit Paracetamol: eine Analyse von 1995 bis 2002. Dtsch Med Wochenschr 128: 15–19

    Article  Google Scholar 

  • Von Mach MA, Weilemann LS (2002) Zunehmende Bedeutung von Antidepressiva bei suizidalen und parasuizidalen Intoxikationen. Dtsch Med Wochenschr 127: 2053–2056

    Article  Google Scholar 

  • Walker IV, Nitiss JL (2002) DNA topoisomerase II as a target for cancer chemotherapy. Cancer Invest 20: 570–589

    Article  Google Scholar 

  • Wallin H, Milkalsen A, Guengerich FP, Ingelman-Sundberg M, Solberg KE, Rossland OJ, Alexander J (1990) Differential rates of metabolic activation and detoxication of the food mutagen 2-amino-l-methyl-6-phenylimidazo[4,5-b]pyridine by different cytochrome P450 enzymes. Carcinogenesis 11:489–492

    Article  Google Scholar 

  • Walter CA, Zhou ZQ, Manguino D, Ikeno Y, Reddick R, Nelson J, Intano G, Herbert DC, McMahan CA, Hanes M (2001) Health span and life span in transgenic mice with modulated DNA repair. Ann NY Acad Sci 928: 132–140

    Article  Google Scholar 

  • Wang JC (2002) Cellular roles of DNA topoisomerases: a molecular perspective. Nat Rev Mol Cell Biol 3: 430–40

    Article  Google Scholar 

  • Ward E, Boffetta P, Andersen A, Colin D, Comba P, Deddens JA, De Santis M, Engholm G, Hagmar L, Langard S, Lundberg I, McElvenny D, Pirastu R, Sali D, Simonato L (2001) Update of the follow-up of mortality and cancer incidence among European workers employed in the vinyl chloride industry. Epidemiology 12: 710–718

    Article  Google Scholar 

  • Waxweiler RJ, Smith AH, Falk H, Tyroler HA (1981) Excess lung cancer risk in a synthetic chemicals plant. Environ Health Perspect 41: 159–165

    Article  Google Scholar 

  • Weber LDW, Lebofsky M, Stahl BU, Gorski JR, Muzi G, Rozman K (1991) Reduced activities of key enzymes of gluconeogenesis as a possible cause of acute toxicity of 2,3,7,8-tetra-chlorodibenzo-p-dioxin (TCDD) in rats. Toxicology 66: 133

    Article  Google Scholar 

  • Weingarten MD, Lockwood AH, Hwo SY, Kirschner MW (1975) A protein factor essential for microtubule assembly. Proc Natl Acad Sci USA 72: 1858–1862

    Article  Google Scholar 

  • Wild CP, Hasegawa R, Barraud L, Chutimataewin S, Chapot B, Nobuyuki I, Montesano R (1996) Aflatoxin-albumin adducts: a basis for comparative carcinogenesis between animals and humans. Cancer Epidemiol Biomarkers Prev 5: 179–189

    Google Scholar 

  • Williams GM, Gebhardt R, Sirma H, Stenback F (1993) Non-linearity of neoplastic conversion induced in rat liver by low exposures to diethylnitrosamine. Carcinogenesis 14: 2149–2156

    Article  Google Scholar 

  • Williams GM, Iatropoulos MJ, Jeffrey AM, Luo FQ, Wang CX, Pittman B (1999) Diethylnitrosamine exposure-responses for DNA ethylation, hepatocellular proliferation, and initiation of carcinogenesis in rat liver display non-linearities and thresholds. Arch Toxicol 73: 394–402

    Article  Google Scholar 

  • Williams GM, Iatropoulos MJ, Jeffrey AM (2000) Mechanistic basis for nonlinearities and thresholds in rat liver carcinogenesis by the DNA-reactive carcinogens 2-acetylaminofluorene and diethylnitrosamine. Toxicol Pathol 28: 388–395

    Article  Google Scholar 

  • Williams GM, Iatropoulos MJ, Wang CX, Ali N, Rivenson A, Peterson LA, Schultz C, Gebhardt R (1996) Diethylnitrosamine exposure-responses for DNA damage, centrilobular cytotoxicity, cell proliferation and carcinogenesis in rat liver exhibit some non-linearities. Carcinogenesis 17: 2253–2258

    Article  Google Scholar 

  • Wilson AS, Williams DP, Davis CD, Tingle MD, Park BK (1997) Bioactivation and inactivation of aflatoxin B1 by human, mouse and rat liver preparations: effect on SCE in human mononuclear leucocytes. Mutat Res 373: 257–264

    Article  Google Scholar 

  • Wilson JD (1997) So carcinogens have thresholds: how do we decide what exposure levels should be considered safe? Risk Anal 17: 1–3

    Article  Google Scholar 

  • Wiltse JA, Dellarco VL (2000) U.S. Environmental Protection Agency’s revised giudelines for carcinogen risk assessment: evaluating a postulated mode of carcinogenic action in guiding dose-response extrapolation. Mutat Res 464: 105–115

    Article  Google Scholar 

  • Wogan GN, Paglialunga S, Newberne PM (1974) Carcinogenic effects of low dietary levels of Aflatoxin B1in rats. Food Cosmet Toxicol. 12: 681–685

    Article  Google Scholar 

  • Wordeman L, Mitchison TJ (1995) Identification and partial characterization of mitotic centromere-associated kinesin, a kinesin-related protein that associates with centromeres during mitosis. J Cell Biology 128: 95–105

    Article  Google Scholar 

  • World Health Organisation [WHO] (1987) Air quality guidelines for Europe. WHO Regional Publications, European Series No. 23, World Health Organisation (WHO) Regional Office, Copenhagen

    Google Scholar 

  • World Health Organisation [WHO] (1999) Guidelines for air quality. World Health Organisation (WHO), Geneva

    Google Scholar 

  • World Health Organisation [WHO] (2000) Air quality guidelines for Europe, 2nd edition. WHO Regional Publications, European Series, No. 91, World Health Organisation (WHO) Regional Office, Copenhagen

    Google Scholar 

  • Wroblewski VJ, Olson JR (1985) Hepatic metabolism of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the rat and guinea pig. Toxicol Appl Pharmacol 81: 231–240

    Article  Google Scholar 

  • Wu MM, Kuo TL, Hwang YH, Chen CJ (1989) Dose-response relation between arsenic concentration in well water and mortality from cancers and vascular diseases. Am J Epidemiol 130: 1123–1132

    Google Scholar 

  • Yager JD, Liehr JG (1996) Molecular mechanisms of oestrogen carcinogenesis. Ann Rev Pharmacol Toxicol 36: 203–232

    Article  Google Scholar 

  • Yamahara H, Lee VHL 1993. Drug metabolism in the oral cavity. Adv Drug Deliv Rev 12: 25–39

    Article  Google Scholar 

  • Yamazoe Y, Abu-Zeid M, Manabe S, Toyama S, Kato R (1988) Metabolic activation of a protein pyrolysate promutagen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline by rat liver microsomes and purified cytochrome P450. Carcinogenesis 9: 105–109

    Article  Google Scholar 

  • Zhou ZQ, Manguino D, Kewitt K, Intano GW, McMahan CA, Herbert DC, Hanes M, Reddick R, Ikeno Y, Walter CA (2001) Spontaneous hepatocellular carcinoma is reduced in transgenic mice overexpressing human O 6-methylguanine-DNA methyltransferase. Proc Natl Acad Sci USA 98: 12566–12571

    Article  Google Scholar 

  • Zober A, Messerer P, Huber P (1990) Thirty-four-year mortality follow-up of BASF employees exposed to 2,3,7,8-TCDD after the 1953 accident. Int Arch Occup Environ Health 62: 139–157

    Article  Google Scholar 

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Streffer, C. et al. (2004). Toxicology of Chemical Carcinogens. In: Wütscher, F. (eds) Low Dose Exposures in the Environment. Wissenschaftsethik und Technikfolgenbeurteilung, vol 23. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-08422-9_4

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