Abstract
Genotoxicity test systems that are based on bacteria display an important role in the detection and assessment of DNA damaging chemicals. They belong to the basic line of test systems due to their easy realization, rapidness, broad applicability, high sensitivity and good reproducibility. Since the development of the Salmonella microsomal mutagenicity assay by Ames and coworkers in the early 1970s, significant development in bacterial genotoxicity assays was achieved and is still a subject matter of research. The basic principle of the mutagenicity assay is a reversion of a growth inhibited bacterial strain, e.g., due to auxotrophy, back to a fast growing phenotype (regain of prototrophy). Deeper knowledge of the mutation events allows a mechanistic understanding of the induced DNA-damage by the utilization of base specific tester strains. Collections of such specific tester strains were extended by genetic engineering. Beside the reversion assays, test systems utilizing the bacterial SOS-response were invented. These methods are based on the fusion of various SOS-responsive promoters with a broad variety of reporter genes facilitating numerous methods of signal detection. A very important aspect of genotoxicity testing is the bioactivation of xenobiotics to DNA-damaging compounds. Most widely used is the extracellular metabolic activation by making use of rodent liver homogenates. Again, genetic engineering allows the construction of highly sophisticated bacterial tester strains with significantly enhanced sensitivity due to overexpression of enzymes that are involved in the metabolism of xenobiotics. This provides mechanistic insights into the toxification and detoxification pathways of xenobiotics and helps explaining the chemical nature of hazardous substances in unknown mixtures. In summary, beginning with “natural” tester strains the rational design of bacteria led to highly specific and sensitive tools for a rapid, reliable and cost effective genotoxicity testing that is of outstanding importance in the risk assessment of compounds (REACH) and in ecotoxicology.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
OECD (1997) Bacterial reverse mutation test. Guideline for Testing of Chemicals 471. OECD, Paris
Müller L, Kikuchi Y, Probst G, Schechtman L, Shimada H, Sofuni T, Tweats D (1999) ICH-Harmonised guidances on genotoxicity testing of pharmaceuticals: evolution, reasoning and impact. Mutat Res 436(3):195–225
OSPAR Commission (2002) Survey on genotoxicity test methods for the evaluation of waste water within whole effluent assessment. OSPAR, London, UK
ISO (2000) Water quality – determination of the genotoxicity of water and waste water using the umu-test. ISO 13829, ISO, Geneva
ISO (2005) Water quality – determination of the genotoxicity of water and waste water – Salmonella/microsome test (Ames test). ISO 16240, ISO, Geneva
International Conference on Harmonization (1997) Guidance for industry. S2B genotoxicity: a standard battery for genotoxicity testing of pharmaceuticals. Brussels, Belgium, March 1997
Hartman PE, Hartman Z, Stahl RC (1971) Classification and mapping of spontaneous and induced mutations in the histidine operon of Salmonella. Adv Genet 16:1–34
Ames BN, Gurney EG, Miller JA, Bartsch H (1972) Carcinogens as frameshift mutagens: metabolites and derivatives of 2-acetylaminofluorene and other aromatic amine carcinogens. Proc Natl Acad Sci U S A 69(11):3128–3132
Ames BN, Durston WE, Yamasaki E, Lee FD (1973) Carcinogens are mutagens: a simple test system combining liver homogenates for activation and bacteria for detection. Proc Natl Acad Sci U S A 70(8):2281–2285
McCann J, Ames BN (1976) Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals: discussion. Proc Natl Acad Sci U S A 73(3):950–954
Jurado J, Alejandre-Durán E, Pueyo C (1993) Genetic differences between the standard Ames tester strains TA100 and TA98. Mutagenesis. 8(6):527-32
McCann J, Spingarn NE, Kobori J, Ames BN (1975) Detection of carcinogens as mutagens: bacterial tester strains with R factor plasmids. Proc Natl Acad Sci U S A 72(3):979–983
Mortelmans K (2006) Isolation of plasmid pKM101 in the Stocker laboratory. Mutat Res 612(3):151–164
Cebula TA, Koch WH (1990) Sequence analysis of Salmonella typhimurium revertants. Prog Clin Biol Res. 340D:367–77. Review
Hartman PE, Ames BN, Roth JR, Barnes WM, Levin DE (1986) Target sequences for mutagenesis in Salmonella histidine-requiring mutants. Environ Mutagen 8(4):631–641
Walker GC (1977) Plasmid (pKM101)-mediated enhancement of repair and mutagenesis: dependence on chromosomal genes in Escherichia coli K-12. Mol Gen Genet 152(1):93–103
Marsh L, Walker GC (1987) New phenotypes associated with mucAB: alteration of a MucA sequence homologous to the LexA cleavage site. J Bacteriol 169(5):1818–1823
Perry KL, Elledge SJ, Mitchell BB, Marsh L, Walker GC (1985) umuDC and mucAB operons whose products are required for UV light- and chemical-induced mutagenesis: UmuD, MucA, and LexA proteins share homology. Proc Natl Acad Sci U S A 82(13):4331–4335
Levin DE, Hollstein M, Christman MF, Schwiers EA, Ames BN (1982) A new Salmonella tester strain (TA102) with A:T base pairs at the site of mutation detects oxidative mutagens. Proc Natl Acad Sci U S A 79(23):7445–7449
Albertini S, Gocke E (1988) Plasmid copy number and mutant frequencies in S. typhimurium TA102. Environ Mol Mutagen 12(4):353–363
Levin DE, Yamasaki E, Ames BN (1982) A new Salmonella tester strain, TA97, for the detection of frameshift mutagens. A run of cytosines as a mutational hot-spot. Mutat Res 94(2):315–330
Bridges BA, Dennis RE, Munson RJ (1967) Differential induction and repair of ultraviolet damage leading to true revesions and external suppressor mutations of an ochre codon in Escherichia coli B-r WP2. Genetics 57(4):897–908
Venturini S, Monti-Bragadin C (1978) R plasmid-mediated enhancement of mutagenesis in strains of Escherichia coli deficient is known repair functions. Mutat Res 50(1):1–8
Prival MJ, King VD, Sheldon AT Jr (1979) The mutagenicity of dialkyl nitrosamines in the Salmonella plate assay. Environ Mutagen 1(2):95–104
Agurell E, Stensman C (1992) Salmonella mutagenicity of three complex mixtures assayed with the microsuspension technique. A WHO/IPCS/CSCM study. Mutat Res 276(1/2):87–91
Bagley ST, Stoltz SL, Becker DM, Keen RE (1992) Characterization of organic extracts from standard reference materials 1649, ‘urban dust/organics,’ and 1650, ‘diesel particulate matter’, using a microsuspension assay. A WHO/IPCS/CSCM study. Mutat Res 276(1/2):81–86
Azuma S, Kishino S, Katayama S, Akahori Y, Matsushita H (1997) Highly sensitive mutation assay for mutagenicity monitoring of indoor air using Salmonella typhimurium YG1041 and a microsuspension method. Mutagenesis 12(5):373–377
Gatehouse DG, Paes DJ (1983) A demonstration of the in vitro bacterial mutagenicity of procarbazine, using the microtitre fluctuation test and large concentrations of S9 fraction. Carcinogenesis 4(3):347–352
Flückiger-Isler S, Baumeister M, Braun K, Gervais V, Hasler-Nguyen N, Reimann R, Van Gompel J, Wunderlich HG, Engelhardt G (2004) Assessment of the performance of the Ames II assay: a collaborative study with 19 coded compounds. Mutat Res 558(1/2):181–197
Reifferscheid G, Arndt C, Schmid C (2005) Further development of the beta-lactamase MutaGen assay and evaluation by comparison with Ames fluctuation tests and the umu test. Environ Mol Mutagen 46(2):126–139
Gee P, Maron DM, Ames BN (1994) Detection and classification of mutagens: a set of base-specific Salmonella tester strains. Proc Natl Acad Sci U S A 91(24):11606–11610
Cupples CG, Miller JH (1989) A set of lacZ mutations in Escherichia coli that allow rapid detection of each of the six base substitutions. Proc Natl Acad Sci U S A 86(14):5345–5349
Miller JE, Vlasakova K, Glaab WE, Skopek TR (2005) A low volume, high-throughput forward mutation assay in Salmonella typhimurium based on fluorouracil resistance. Mutat Res 578(1/2):210–224
Dorado G, Pueyo C (1988) l-Arabinose resistance test with Salmonella typhimurium as a primary tool for carcinogen screening. Cancer Res 48(4):907–912
Schmid C, Arndt C, Reifferscheid G (2003) Mutagenicity test system based on a reporter gene assay for short-term detection of mutagens (MutaGen assay). Mutat Res 535(1):55–72
Tomasz A (1979) From penicillin-binding proteins to the lysis and death of bacteria: a 1979 view. Rev Infect Dis 1(3):434–467
Tomasz A (1979) The mechanism of the irreversible antimicrobial effects of penicillins: how the beta-lactam antibiotics kill and lyse bacteria. Annu Rev Microbiol 33:113–137
Hillen W, Berens C (1994) Mechanisms underlying expression of TN10 encoded tetracycline resistance. Annu Rev Microbiol 48:345–369
Degenkolb J, Takahashi M, Ellestad GA, Hillen W (1991) Structural requirements of tetracycline-tet repressor interaction: determination of equilibrium binding constants for tetracycline analogs with the tet repressor. Antimicrob Agents Chemother 35:1591–1595
Radman M (1975) SOS repair hypothesis: phenomenology of an inducible DNA repair which is accompanied by mutagenesis. Basic Life Sci 5A:355–367
Brent R, Ptashne M (1980) The lexA gene product represses its own promoter. Proc Natl Acad Sci U S A 77(4):1932–1936
Little JW, Mount DW, Yanisch-Perron CR (1981) Purified lexA protein is a repressor of the recA and lexA genes. Proc Natl Acad Sci U S A 78(7):4199–4203
Little JW (1983) The SOS regulatory system: control of its state by the level of RecA protease. J Mol Biol 167(4):791–808
Little JW, Edmiston SH, Pacelli LZ, Mount DW (1980) Cleavage of the Escherichia coli lexA protein by the recA protease. Proc Natl Acad Sci U S A 77(6):3225–3229
Giese KC, Michalowski CB, Little JW (2008) RecA-dependent cleavage of LexA dimers. J Mol Biol 377(1):148–161
Huisman O, D’Ari R, George J (1980) Further characterization of sfiA and sfiB mutations in Escherichia coli. J Bacteriol 144(1):185–191
Schendel PF, Fogliano M, Strausbaugh LD (1982) Regulation of the Escherichia coli K-12 uvrB operon. J Bacteriol 150(2):676–685
Frey J, Ghersa P, Palacios PG, Belet M (1986) Physical and genetic analysis of the ColD plasmid. J Bacteriol. 166(1):15–9
Tomita K, Ogawa T, Uozumi T, Watanabe K, Masaki H (2000) A cytotoxic ribonuclease which specifically cleaves four isoaccepting arginine tRNAs at their anticodon loops. Proc Natl Acad Sci U S A 97(15):8278–8283
de Zamaroczy M, Mora L, Lecuyer A, Géli V, Buckingham RH (2001) Cleavage of colicin D is necessary for cell killing and requires the inner membrane peptidase LepB. Mol Cell 8(1):159–168
Quillardet P, Huisman O, D’Ari R, Hofnung M (1982) SOS chromotest, a direct assay of induction of an SOS function in Escherichia coli K-12 to measure genotoxicity. Proc Natl Acad Sci U S A 79(19):5971–5975
da Y, Nakamura S, Oki I, Kato T, Shinagawa H (1985) Evaluation of the new system (umu-test) for the detection of environmental mutagens and carcinogens. Mutat Res 147(5):219–229
Ptitsyn LR, Horneck G, Komova O, Kozubek S, Krasavin EA, Bonev M, Rettberg P (1997) A biosensor for environmental genotoxin screening based on an SOS lux assay in recombinant Escherichia coli cells. Appl Environ Microbiol. 63(11):4377–84
Norman A, Hestbjerg Hansen L, Sørensen SJ (2005) Construction of a ColD cda promoter-based SOS-green fluorescent protein whole-cell biosensor with higher sensitivity toward genotoxic compounds than constructs based on recA, umuDC, or sulA promoters. Appl Environ Microbiol 71(5):2338–2346
Nunoshiba T, Nishioka H (1991) ‘Rec-lac test’ for detecting SOS-inducing activity of environmental genotoxic substance. Mutat Res 254(1):71–77
Verschaeve L, Van Gompel J, Thilemans L, Regniers L, Vanparys P, van der Lelie D (1999) VITOTOX bacterial genotoxicity and toxicity test for the rapid screening of chemicals. Environ Mol Mutagen 33(3):240–248
Vollmer AC, Belkin S, Smulski DR, Van Dyk TK, LaRossa RA (1997) Detection of DNA damage by use of Escherichia coli carrying recA’::lux, uvrA’::lux or alkA’::lux reporter plasmids. Appl Environ Microbiol 63:2566–2571
Davidov Y, Rozen R, Smulski DR, van Dyk TK, Vollmer AC, Elsemore DA, LaRossa RA, Belkin S (2000) Improved bacterial SOS promoter: lux fusions for genotoxicity detection. Mutat Res 466:97–107
Chalfie M, Tu G, Euskirchen G, Ward WW, Prasher DC (1994) Green fluorescent protein as a marker for gene expression. Science 263:802–804
Crameri A, Whitehorn EA, Tate E, Stemmer WPC (1996) Improved green fluorescent protein by molecular evolution using DNA shuffling. Nat Biotechnol 14:315–319
Arkady FF, Ying C, Li D, Ekaterina VB, Mikhail VM, Sergey AL (2000) Novel fluorescent protein from Discosoma coral and its mutants possesses a unique far-red fluorescence. FEBS Lett 479:127–130
Shaner NC, Patterson GH, Davidson MW (2007) Advances in fluorescent protein technology. J Cell Sci 120:4247–4260
Nagai T, Ibata K, Park ES, Kubota M, Mikoshiba K, Miyawaki A (2002) A variant of yellow fluorescent protein with fast and efficient maturation for cell-biological applications. Nat Biotechnol 20:87–90
Blokpoel MC, O’Toole R, Smeulders MJ, Williams HD (2003) Development and application of unstable GFP variants to kinetic studies of mycobacterial gene expression. J Microbiol Methods 54:203–211
Justus T, Thomas SM (1999) Evaluation of transcriptional fusions with green fluorescent protein versus luciferase as reporters in bacterial mutagenicity tests. Mutagenesis 14:351–356
Arai R, Makita Y, Oda Y, Nagamune T (2001) Construction of green fluorescent protein reporter genes for genotoxicity test (SOS/umu-test) and improvement of mutagen-sensitivity. J Biosci Bioeng 92:301–304
Kostrzynska M, Leung KT, Lee H, Trevors JT (2002) Green fluorescent protein-based biosensor for detecting SOS-inducing activity of genotoxic compounds. J Microbiol Methods 48:43–51
Sagi E, Hever N, Rosen R, Bartolome AJ, Rajan Premkumar J, Ulber R, Lev O, Scheper T, Belkin S (2003) Fluorescence and bioluminescence reporter functions in genetically modified bacterial sensor strains. Sens Actuators B Chem 90:2–8
Hakkila K, Maksimow M, Karp M, Virta M (2002) Reporter genes lucFF, luxCDABE, gfp, and dsred have different characteristics in whole-cell bacterial sensors. Anal Biochem 301:235–242
Norman A, Hansen LH, Sorensen SJ (2006) A flow cytometry-optimized assay using an SOS-green fluorescent protein (SOS-GFP) whole-cell biosensor for the detection of genotoxins in complex environments. Mutat Res 603(2):164–172
Ostergaard TG, Hansen LH, Binderup ML, Norman A, Sørensen SJ (2007) The cda GenoTox assay: a new and sensitive method for detection of environmental genotoxins, including nitroarenes and aromatic amines. Mutat Res 631(2):77–84
von der Hude W, Behm C, Gürtler R, Basler A (1988) Evaluation of the SOS chromotest. Mutat Res 203(2):81–94
Dipple A (1995) DNA adducts of chemical carcinogens. Carcinogenesis 16(3):437–441
Seidegard J, Ekstrom G (1997) The role of human glutathione transferases and epoxide hydrolases in the metabolism of xenobiotics. Environ Health Perspect 105(4):791–799
Kranendonk M, Laires A, Rueff J, Estabrook WR, Vermeulen NP (2000) Heterologous expression of xenobiotic mammalian-metabolizing enzymes in mutagenicity tester bacteria: an update and practical considerations. Crit Rev Toxicol 30:287–306
Shimada T, Yamazaki H, Oda Y, Hiratsuka A, Watabe T, Guengerich FP (1996) Activation and inactivation of carcinogenic dihaloalkanes and other compounds by glutathione S-transferase 5-5 in Salmonella typhimurium tester strain NM5004. Chem Res Toxicol 9:333–340
Martignoni M, Groothuis GM, de Kanter R (2006) Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Expert Opin Drug Metab Toxicol 2(6):875–894
Gundert-Remy U, Sonich-Mullin C (2002) IPCS uncertainty and variability planning workgroup and drafting group (International program on chemical safetys). The use of toxicokinetic and toxicodynamic data in risk assessment: an international perspective. Sci Total Environ 288(1/2):3–11
Malling HV (1967) The mutagenicity of the acridine mustard (ICR-170) and the structurally related compounds in Neurospora. Mutat Res 4(3):265–274
Glatt H (1997) Sulfation and sulfotransferases 4: bioactivation of mutagens via sulfation. FASEB J 11(5):314–321
Guengerich FP (2006) Cytochrome P450s and other enzymes in drug metabolism and toxicity. AAPS J 8(1):101–111
Roberts GA, Grogan G, Greter A, Flitsch SL, Turner NJ (2002) Identification of a new class of cytochrome P450 from a Rhodococcus sp. J Bacteriol 184(14):3898–3908
Agematu H, Matsumoto N, Fujii Y, Kabumoto H, Doi S, Machida K, Ishikawa J, Arisawa A (2006) Hydroxylation of testosterone by bacterial cytochromes P450 using the Escherichia coli expression system. Biosci Biotechnol Biochem 70(1):307–311
Dong J, Porter TD (1996) Coexpression of mammalian cytochrome P450 and reductase in Escherichia coli. Arch Biochem Biophys 327(2):254–259
Blake JA, Pritchard M, Ding S, Smith GC, Burchell B, Wolf CR, Friedberg T (1996) Coexpression of a human P450 (CYP3A4) and P450 reductase generates a highly functional monooxygenase system in Escherichia coli. FEBS Lett 397(2/3):210–214
Shet MS, Fisher CW, Estabrook RW (1997) The function of recombinant cytochrome P450s in intact Escherichia coli cells: the 17 alpha-hydroxylation of progesterone and pregnenolone by P450c17. Arch Biochem Biophys 339(1):218–225
Parikh A, Gillam EM, Guengerich FP (1997) Drug metabolism by Escherichia coli expressing human cytochromes P450. Nat Biotechnol 15(8):784–788
Emmert B, Bünger J, Keuch K, Müller M, Emmert S, Hallier E, Westphal GA (2006) Mutagenicity of cytochrome P450 2E1 substrates in the Ames test with the metabolic competent S. typhimurium strain YG7108pin3ERb5. Toxicology 228(1):66–76
Aryal P, Yoshikawa K, Terashita T, Guengerich FP, Shimada T, Oda Y (1999) Development of a new genotoxicity test system with Salmonella typhimurium OY1001/1A2 expressing human CYP1A2 and NADPH-P450 reductase. Mutat Res 442(2):113–120
Oda Y, Aryal P, Terashita T, Gillam EM, Guengerich FP, Shimada T (2001) Metabolic activation of heterocyclic amines and other procarcinogens in Salmonella typhimurium umu tester strains expressing human cytochrome P4501A1, 1A2, 1B1, 2C9, 2D6, 2E1, and 3A4 and human NADPH-P450 reductase and bacterial O-acetyltransferase. Mutat Res 492(1/2):81–90
Aryal P, Terashita T, Guengerich FP, Shimada T, Oda Y (2000) Use of genetically engineered Salmonella typhimurium OY1002/1A2 strain coexpressing human cytochrome P450 1A2 and NADPH-cytochrome P450 reductase and bacterial O-acetyltransferase in SOS/umu assay. Environ Mol Mutagen 36(2):121–126
Sugimura T (1997) Overview of carcinogenic heterocyclic amines. Mutat Res 376(1/2):211–219
Kataoka H (1997) Methods for the determination of mutagenic heterocyclic amines and their applications in environmental analysis. J Chromatogr A 774(1/2):121–142
Oda Y, Shimada T, Watanabe M, Ishidate M Jr, Nohmi T (1992) A sensitive umu test system for the detection of mutagenic nitroarenes in Salmonella typhimurium NM1011 having a high nitroreductase activity. Mutat Res 272(2):91–99
Oda Y, Yamazaki H, Watanabe M, Nohmi T, Shimada T (1995) Development of high sensitive umu test system: rapid detection of genotoxicity of promutagenic aromatic amines by Salmonella typhimurium strain NM2009 possessing high O-acetyltransferase activity. Mutat Res 334(2):145–156
Oda Y, Yamazaki H, Shimada T (1999) Role of human N-acetyltransferases, NAT1 or NAT2, in genotoxicity of nitroarenes and aromatic amines in Salmonella typhimurium NM6001 and NM6002. Carcinogenesis 20(6):1079–1083
Oda Y, Yamazaki H, Thier R, Ketterer B, Guengerich FP, Shimada T (1996) A new Salmonella typhimurium NM5004 strain expressing rat glutathione S-transferase 5-5: use in detection of genotoxicity of dihaloalkanes using an SOS/umu test system. Carcinogenesis 17(2):297–302
Watanabe M, Ishidate M Jr, Nohmi T (1989) A sensitive method for the detection of mutagenic nitroarenes: construction of nitroreductase-overproducing derivatives of Salmonella typhimurium strains TA98 and TA100. Mutat Res 216(4):211–220
Watanabe M, Ishidate M Jr, Nohmi T (1990) Sensitive method for the detection of mutagenic nitroarenes and aromatic amines: new derivatives of Salmonella typhimurium tester strains possessing elevated O-acetyltransferase levels. Mutat Res 234(5):337–348
Hagiwara Y, Watanabe M, Oda Y, Sofuni T, Nohmi T (1993) Specificity and sensitivity of Salmonella typhimurium YG1041 and YG1042 strains possessing elevated levels of both nitroreductase and acetyltransferase activity. Mutat Res 291(3):171–180
Chasseaud LF (1997) The role of glutathione ans glutathione transferases in the metabolism of chemical carcinogens and other electrophilic reagents. Adv Cancer Res 29:175–274
Coles B, Ketterer B (1990) The role of glutathione and glutathione transfersase in chemical carcinogenesis. Crit Rev Biochem Mol Biol 25:47–70.
Decant W, Vamvakas S, Anders MW (1989) Bioactivation of nephrotoxic haloalkenes by glutathiuone conjugation: formation of toxic and mutagenic intermediates by cysteine conjugate ß-lyase. Drug Metab Rev 20:43–83
Monks TJ, Lau SS (1994) Glutathione conjugate mediated toxicities. In: Kauffman FC (ed) Handbook of experimental pharmacology. Springer, Berlin Heidelberg New York, pp 459–509
Thier R, Taylor JB, Pemble SE, Humphreys WG, Persmark M, Ketterer B, Guengerich FP (1993) Expression of mammalian glutathione S-transferase 5-5 in Salmonella typhimurium TA1535 leads to base-pair mutations upon exposure to dihalomethanes. Proc Natl Acad Sci U S A 90(18):8576–8580
Guengerich FP, Wheeler JB, Chun YJ, Kim D, Shimada T, Aryal P, Oda Y, Gillam EM (2002) Use of beterologously-expressed cytochrome P450 and glutathione transferase enzymes in toxicity assays. Toxicology 181–182:261–4
Pemble S, Schroeder KR, Spencer SR, Meyer DJ, Hallier E, Bolt HM, Ketterer B, Taylor JB (1994) Human glutathione S-transferase theta (GSTT1): cDNA cloning and the characterization of a genetic polymorphism. Biochem J 300(1):271–276
Yamazaki H, Oda Y, Shimada T (1992) Use of a newly developed tester strain Salmonella typhimurium NM2009 for the study of metabolic activation of carcinogenic aromatic amines by rat liver microsomal cytochrome P-450 enzymes. Mutat Res 272(2):183–192
Lotlikar PD, Hong YS (1981) Microsomal N- and C-oxidations of carcinogenic aromatic amines and amides. Natl Cancer Inst Monogr 58:101–107
McCoy EC, Anders M, Rosenkranz HS (1983) The basis of the insensitivity of Salmonella typhimurium strain TA98/1,8-DNP6 to the mutagenic action of nitroarenes. Mutat Res 121(1):17–23
Heflich RH, Djurić Z, Zhuo Z, Fullerton NF, Casciano DA, Beland FA (1988) Metabolism of 2-acetylaminofluorene in the Chinese hamster ovary cell mutation assay. Environ Mol Mutagen 11(2):167–181
Lower GM Jr, Nilsson T, Nelson CE, Wolf H, Gamsky TE, Bryan GT (1979) N-Acetyltransferase phenotype and risk in urinary bladder cancer: approaches in molecular epidemiology. Preliminary results in Sweden and Denmark. Environ Health Perspect 29:71–79
Lang NP, Chu DZ, Hunter CF, Kendall DC, Flammang TJ, Kadlubar FF (1986) Role of aromatic amine acetyltransferase in human colorectal cancer. Arch Surg 121(11):1259–1261
Glatt H, Meinl W (2005) Sulfotransferases and acetyltransferases in mutagenicity testing: technical aspects. Methods Enzymol 400:230–249
Miller JA, Surh YJ (1994) Sulfonation in chemical carcinogenes. In: Kauffman FC (ed) Handbook of pharmacology, vol 112: Conjugation-deconjugation reactions in drug metabolism and toxicity. Springer, Berlin Heidelberg New York, pp 429–458
Suzuki H, Morris JS, Li Y, Doll MA, Hein DW, Liu J, Jiao L, Hassan MM, Day RS, Bondy ML, Abbruzzese JL, Li D (2008) Interaction of the cytochrome P4501A2, SULT1A1 and NAT gene polymorphisms with smoking and dietary mutagen intake in modification of the risk of pancreatic cancer. Carcinogenesis 29(6):1184–1191
Glatt H (2005) Activation and inactivation of carcinogens by human sulfotransferases. In: Pacifici GM, Coughtrie MWH (eds) Human sulfotransferases. Taylor & Francis, London
Glatt H, Meinl W (2004) Use of genetically manipulated Salmonella typhimurium strains to evaluate the role of sulfotransferases and acetyltransferases in nitrofen mutagenicity. Carcinogenesis 25(5):779–786
Tokiwa H, Ohnishi Y (1986) Mutagenicity and carcinogenicity of nitroarenes and their sources in the environment. Crit Rev Toxicol 17(1):23–60
Wild D (1990) A novel pathway to the ultimate mutagens of aromatic amino and nitro compounds. Environ Health Perspect 88:27–31
Oda Y, Yamazaki H, Watanabe M, Nohmi T, Shimada T (1993) Highly sensitive umu test system for the detection of mutagenic nitroarenes in Salmonella typhimurium NM3009 having high O-acetyltransferase and nitroreductase activities. Environ Mol Mutagen 21(4):357–364
Guengerich FP, Wheeler JB, Chun YJ, Kim D, Shimada T, Aryal P, Oda Y, Gillam EM (2002) Use of heterologously-expressed cytochrome P450 and glutathione transferase enzymes in toxicity assays. Toxicology 181/182:261–264
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Reifferscheid, G., Buchinger, S. (2009). Cell-Based Genotoxicity Testing. In: Belkin, S., Gu, M. (eds) Whole Cell Sensing System II. Advances in Biochemical Engineering / Biotechnology, vol 118. Springer, Berlin, Heidelberg. https://doi.org/10.1007/10_2009_8
Download citation
DOI: https://doi.org/10.1007/10_2009_8
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-12852-3
Online ISBN: 978-3-642-12853-0
eBook Packages: Chemistry and Materials ScienceChemistry and Material Science (R0)