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Comparison of CYP1A1 induction and genotoxicity in vitro as indicators of potentially harmful effects of environmental samples

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Abstract

Cytochrome P450IA1 (CYP1A1) induction of Hepa-1 mouse and H4IIE rat hepatoma cell lines was compared using selected environmental samples. The results were in agreement for both cell lines: no induction was observed for the fly ash extract from peat combustion, an intermediate induction was found for the fly ash extract from biosludge combustion, and a strong induction was detected for natural peat extract. However, Hepa-1 responded to the samples more sensitively than did H4IIE: the half maximal induction (ED50) values for Hepa-1 were smaller than those for H4IIE. In a bacterial DNA repair assay without metabolic activation and in a mammalian sister chromatid exchange test in the presence of metabolic activation the samples were virtually non-genotoxic. Thus the CYP1A1-inducing potency and genotoxicity of the samples were not correlated. In light of these results, the CYP1A1 induction test might be a useful addition to conventional genotoxicity tests, which may fail to detect potentially harmful compounds/mixtures.

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References

  • Ahlborg UG, Brouwer A, Fingerhut MA, Jacobson JL, Jacobson SW, Kennedy SW, Kettrup AAF, Koeman JH, Poiger H, Rappe C, Safe SH, Seegal RF, Tuomisto J, van den Berg M (1992) Impact of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls on human and environmental health, with special emphasis on application of the toxic equivalency factor concept. Eur J Pharmacol 228: 179–199

    PubMed  CAS  Google Scholar 

  • Arey J, Harger WP, Helmig D, Atkinson R (1992) Bioassay-directed fractionation of mutagenic PAH atmospheric photooxidation products and ambient particulate extracts. Mutat Res 281: 67–76

    Article  PubMed  CAS  Google Scholar 

  • Ashby J (1992) Use of short-term tests in determining the genotoxicity or nongenotoxicity of chemicals. In: Vainio H, Magee PN, McGregor DB, McMichael AJ (eds) Mechanism of carcinogenesis in risk identification. IARC Sci Publ, no 116, Oxford University Press, Oxford, pp 135–164

    Google Scholar 

  • Bernhard HP, Darlington GJ, Ruddle FJ (1973) Expression of liver phenotypes in cultured mouse hepatoma cells: synthesis and secretion of serum albumin. Dev Biol 35: 83–96

    Article  PubMed  CAS  Google Scholar 

  • Buser H-R (1975) Analysis of polychlorinated dibenzo-p-dioxins and dibenzofurans in chlorinated phenols by mass fragmentography. J Chromatogr 107: 295–310

    Article  PubMed  CAS  Google Scholar 

  • Carrier F, Owens RA, Nebert DW, Puga A (1992) Dioxin-dependent activation of murineCyp1a-1 gene transcription requires protein kinase C-dependent phosphorylation. Mol Cell Biol 12: 1856–1863

    PubMed  CAS  Google Scholar 

  • Chou MW, Wang B, von Tungeln LS, Beland FA, Fu PP (1987) Induction of rat hepatic cytochromes P-450 by environmental nitropolycyclic aromatic hydrocarbons. Biochem Pharmacol 36: 2449–2454

    Article  PubMed  CAS  Google Scholar 

  • Ewetz L, Camner P (1983) (eds) Health risks resulting from exposure to motor vehicle exhaust. A report to the Swedish Government Committee on Automotive Air Pollution, National Swedish Institute of Environmental Medicine, Stockholm, p 203

    Google Scholar 

  • Fujii-Kuriyama Y, Imataka H, Sogawa K, Yasumoto K-I, Kikuchi Y (1992) Regulation ofCYP1A1 expression. FASEB J 6: 706–710

    PubMed  CAS  Google Scholar 

  • Goldstein JA, Safe S (1989) Mechanism of action and structure-activity relationships for the chlorinated dibenzo-p-dioxins and related compounds. In: Kimbrough RD, Jensen AA (eds) Halogenated biphenyls, terphenyls, naphthalenes, dibenzodioxins and related products. Elsevier, Amsterdam, pp 239–293.

    Google Scholar 

  • Hanberg A, Ståhlberg M, Georgellis A, de Wit C, Ahlborg UG (1991) Swedish dioxin survey: evaluation of the H-4-II E bioassay for screening environmental samples for dioxin-like enzyme induction. Pharmacol Toxicol 69: 442–449

    Article  PubMed  CAS  Google Scholar 

  • Hankinson O (1979) Single-step selection of clones of a mouse hepatoma line deficient in aryl hydrocarbon hydroxylase. Proc Natl Acad Sci USA 76: 373–376

    Article  PubMed  CAS  Google Scholar 

  • Hankinson O (1980) Unstable aryl hydrocarbon hydroxylase-deficient variants of a rat hepatoma line. Somat Cell Genet 6: 751–767

    Article  PubMed  CAS  Google Scholar 

  • Hankinson O, Brooks BA, Weir-Brown KI, Hoffman EC, Johnson BS, Nanthur J, Reyes H, Watson AJ (1991) Genetic and molecular analysis of the Ah receptor andCyp1a1 gene expression. Biochimie 73: 61–66

    Article  PubMed  CAS  Google Scholar 

  • Harris WR, Remsen JF, Chess EK, Later DW (1987) Correlation of nitroaromatic compounds with the mutagenic activity of coal fly ash. J Toxicol Environ Health 20: 81–103

    Article  PubMed  CAS  Google Scholar 

  • Helmig D, Arey J, Harger WP, Atkinson R, Lopez-Cancio J (1992) Formation of mutagenic nitrobenzopyranones and their occurrence in ambient air. Environ Sci Technol 26: 622–624

    Article  CAS  Google Scholar 

  • Houk VS, Goto S, Endo O, Claxton LD, Lewtas J, Matsushita H (1992) Detection of direct-acting mutagens in ambient-air: a comparison of two highly sensitive mutagenicity assays. Environ Mol Mutagen 20: 19–28

    Article  PubMed  CAS  Google Scholar 

  • Ioannides C (1990) Induction of cytochrome P450I and its influences in chemical carcinogenesis. Biochem Soc Trans 18: 32–34

    PubMed  CAS  Google Scholar 

  • Ioannides C, Parke DV (1987) The cytochromes P-448 — a unique family of enzymes involved in chemical toxicity and carcinogenesis. Biochem Pharmacol 36: 4197–4207

    Article  PubMed  CAS  Google Scholar 

  • Kärenlampi S (1987) Mechanism of cytotoxicity of aflatoxin B1: role of cytochrome P1-450. Biochem Biophys Res Commun 145: 854–860

    Article  PubMed  Google Scholar 

  • Kärenlampi S, Törrönen R (1990) Induction of cytochrome P450IA1 in mouse hepatoma cells as a short-term bioassay. ATLA 17: 158–162

    Google Scholar 

  • Kärenlampi SO, Tuomi K, Korkalainen M, Raunio H (1989) Induction of cytochrome P450IA1 in mouse hepatoma cells by several chemicals. Phenobarbital and TCDD induce the same form of cytochrome P450. Biochem Pharmacol 38: 1517–1525

    Article  PubMed  Google Scholar 

  • Kopponen P, Törrönen R, Tarhanen J, Ruuskanen J, Kärenlampi S (1991) Cytochrome P450IA1 induction in mouse hepatoma cell culture as an indicator of polycyclic organic compounds in fly ash. Chemosphere 22: 895–904

    Article  CAS  Google Scholar 

  • Kopponen P, Mannila E, Kärenlampi S (1992a) Induction of aryl hydrocarbon hydroxylase AHH by two previously uncharacterized pentachlorinated biphenyls in a mouse and a rat hepatoma cell line. Chemosphere 24: 201–210

    Article  Google Scholar 

  • Kopponen P, Törrönen R, Ruuskanen J, Tarhanen J, Vartiainen T, Kärenlampi S (1992b) Comparison of cytochrome P450IA1 induction with the chemical composition of fly ash from combustion of chlorine containing material. Chemosphere 24: 391–401

    Article  CAS  Google Scholar 

  • Kopponen P, Tarhanen J, Ruuskanen J, Törrönen R, Kärenlampi S (1993) Peat induces cytochrome P450IA1 in Hepa-1 cell line. Comparison with fly ashes from combustion of peat, coal, heavy fuel oil and hazardous waste. Chemosphere 26: 1499–1506

    Article  CAS  Google Scholar 

  • Landers JP, Bunce NJ (1991) TheAh receptor and the mechanism of dioxin toxicity. Biochem J 276: 273–287

    PubMed  CAS  Google Scholar 

  • Lewtas J (1989) Emerging methodologies for assessment of complex mixtures: application of bioassays in the integrated air cancer project. Toxicol Ind Health 5: 839–850

    PubMed  CAS  Google Scholar 

  • Lipp H-P, Schrenk D, Wiesmüller T, Hagenmaier H, Bock KW (1992) Assessment of biological activities of mixtures of polychlorinated dibenzo-p-dioxin (PCDDs) and their constituents in human HepG2 cells. Arch Toxicol 66: 220–223

    Article  PubMed  CAS  Google Scholar 

  • Lucier GW (1992) Receptor-mediated carcinogenesis. In: Vainio H, Magee PN, McGregor DB, McMichael AJ (eds) Mechanisms of carcinogenesis in risk identification. IARC Sci Publ, vol 116, Oxford University Press, Oxford, pp 87–112

    Google Scholar 

  • Löfroth G, Toftgård R, Nilsson L, Agurell E, Gustafsson J-Å (1984) Short-term bioassays of nitro derivates of benzo[a]pyrene and perylene. Carcinogenesis 5: 925–930

    Article  PubMed  Google Scholar 

  • Maron DM, Ames BN (1983) Revised methods for the Salmonella mutagenicity test. Mutat Res 113: 173–215

    PubMed  CAS  Google Scholar 

  • Merchant M, Wang X, Kamps C, Rosengren R, Morrison V, Safe S (1992) Mechanism of benzo[a]pyrene-inducedCyp1a-1 gene expression in mouse Hepa 1c1c7 cells: role of the nuclear 6 s and 4 s proteins. Arch Biochem Biophys 292: 250–257

    Article  PubMed  CAS  Google Scholar 

  • Nebert DW (1989) TheAh locus: genetic differences in toxicity, cancer, mutation, and birth defects. Crit Rev Toxicol 20: 153–174

    Article  PubMed  CAS  Google Scholar 

  • Perdew GH (1992) Chemical cross-linking of the cytosolic and nuclear forms of theAh receptor in hepatoma cell line 1c1c7. Biochem Biophys Res Commun 182: 55–62

    Article  PubMed  CAS  Google Scholar 

  • Pongratz I, Mason GGF, Poellinger L (1992) Dual roles of the 90-kDa heat shock protein hsp90 in modulating functional activities of the dioxin receptor. Evidence that the dioxin receptor functionally belongs to a subclass of nuclear receptors which require hsp90 both for ligand binding activity and repression of intrinsic DNA binding activity. J Biol Chem 267: 13728–13734

    PubMed  CAS  Google Scholar 

  • Rappe C, Buser HR (1989) Chemical and physical properties, analytical methods, sources and environmental levels of halogenated dibenzodioxins and dibenzofurans. In: Kimbrough RD, Jensen AA (eds) Halogenated biphenyls, terphenyls, naphthalenes, dibenzodioxins and related products. Elsevier, Amsterdam, pp 71–102

    Google Scholar 

  • Safe S (1989) Risk assessment of PCDDs and PCDFs based on in vitro and in vivo bioassays. Chemosphere 19: 609–613

    Article  Google Scholar 

  • Safe S (1990) Polychlorinated biphenyls (PCBS), dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and related compounds: environmental and mechanistic considerations which support the development of toxic equivalency factors (TEFs). Crit Rev Toxicol 21: 51–88

    Article  PubMed  CAS  Google Scholar 

  • Safe S, Mason G, Farrell K, Keys B, Piskorska-Pliszczynska J, Madge JA, Chittim B (1987) Validation of in vitro bioassays for 2,3,7,8-TCDD equivalents. Chemosphere 16: 1723–1728

    Article  CAS  Google Scholar 

  • Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning, a laboratory manual, Book 3, A. 3. Cold Spring Harbor Laboratory Press, USA

    Google Scholar 

  • Schaefer EL, Au WW, Selkirk JK (1985) Differential induction of sister-chromatid exchanges by benzo[a]pyrene in variant mouse hepatoma cells. Mutat Res 143: 69–74

    Article  PubMed  CAS  Google Scholar 

  • Schrenk D, Lipp H-P, Wiesmüller T, Hagenmaier H, Bock KW (1991) Assessment of biological activities of mixtures of polychlorinated dibenzo-p-dioxin: comparison between defined mixtures and their constituents. Arch Toxicol 65: 114–118

    Article  PubMed  CAS  Google Scholar 

  • Silbergeld EK, Gasiewicz TA (1989) Dioxins and the Ah receptor. Am J Ind Med 16: 455–474

    Article  PubMed  CAS  Google Scholar 

  • Silkowski MA, Smith SR, Plewa MJ (1992) Analysis of the genotoxicity of municipal solid waste incinerator ash. Sci Total Environ 111: 109–124

    Article  PubMed  CAS  Google Scholar 

  • Skene SA, Dewhurst IC, Greenberg M (1989) Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans: the risks to human health. Hum Toxicol 8: 173–203

    Article  PubMed  CAS  Google Scholar 

  • Tillitt DE, Giesy JP, Ankley GT (1991) Characterization of the H4IIE rat hepatoma cell bioassay as a tool for assessing toxic potency of planar halogenated hydrocarbons in environmental samples. Environ Sci Technol 25: 87–92

    Article  CAS  Google Scholar 

  • Turteltaub KW, Felton JS, Gledhill BL, Vogel JS, Southon JR, Caffee MW, Finkel RC, Nelson DE, Proctor ID, Davis JC (1990) Accelerator mass spectrometry in biomedical dosimetry: relationship between low-level exposure and covalent binding of heterocyclic amine carcinogens to DNA. Proc Natl Acad Sci USA 87: 5288–5292

    Article  PubMed  CAS  Google Scholar 

  • Tweats DJ, Green HHL, Muriel W (1981) A differential killing assay for mutagens and carcinogens based on an improved repair-deficient strain ofEscherichia coli. Carcinogenesis 2: 189–194

    Article  PubMed  CAS  Google Scholar 

  • Watson AJ, Hankinson O (1992) Dioxin- andAh receptor-dependent protein binding to xenobiotic responsive elements and G-rich DNA studied by in vivo footprinting. J Biol Chem 266: 6874–6878

    Google Scholar 

  • von Wright A, Raatikainen O, Taipale H, Kärenlampi S, Mäki-Paakkanen J (1992) Directly acting geno- and cytotoxic agents from a wild mushroomDermocybe sanguinea. Mutat Res 269: 27–33

    Google Scholar 

  • Wu L, Whitlock Jr JP (1992) Mechanism of dioxin action: Ah receptor-mediated increase in promoter accessibility in vivo. Proc Natl Acad Sci 89: 4811–4815

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Physiology, University of Kuopio, PO Box 1627, FIN-70211, Kuopio, Finland

    Päivi Kopponen & Riitta Törrönen

  2. Department of Toxicology, National Public Health Institute, PO Box 95, FIN-70211, Kuopio, Finland

    Jorma Mäki-Paakkanen

  3. Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, FIN-70211, Kuopio, Finland

    Atte von Wright

  4. Department of Biochemistry and Biotechnology, University of Kuopio, PO Box 1627, FIN-70211, Kuopio, Finland

    Sirpa Kärenlampi

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  1. Päivi Kopponen
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  2. Riitta Törrönen
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  5. Sirpa Kärenlampi
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Kopponen, P., Törrönen, R., Mäki-Paakkanen, J. et al. Comparison of CYP1A1 induction and genotoxicity in vitro as indicators of potentially harmful effects of environmental samples. Arch Toxicol 68, 167–173 (1994). https://doi.org/10.1007/s002040050050

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  • DOI: https://doi.org/10.1007/s002040050050

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