Genotoxicity of 2,6- and 3,5-dimethylaniline in cultured mammalian cells: The role of reactive oxygen species

Toxicological Sciences

Volumn 130, Issue 1, 2012, Pages 48-59

  Chao, Ming Wei ^a   Kim, Min Young ^b   Ye, Wenjie ^a   Ge, Jing ^a   Trudel, Laura J ^a   Belanger, Crystal L ^a   Skipper, Paul L ^a   Engelward, Bevin P ^a   Tannenbaum, Steven R ^a,c   Wogan, Gerald N ^a,c  

^a Massachusetts Institute of Technology   (United States)

^b Jeju National University   (South Korea)

^c MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

Alkylanilines; CHO cells; Comet assay; Dimethylaniline; DNA strand breaks; Mutations; Reactive oxygen species

Indexed keywords

2,6 DIMETHYLANILINE; 3,5 DIMETHYLANILINE; ADENINE PHOSPHORIBOSYLTRANSFERASE; AMINOPHENOL; ARYLAMINE ACETYLTRANSFERASE; CYTOCHROME P450 1A2; HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE; INDOPHENOL; N,N DIMETHYLANILINE; REACTIVE OXYGEN METABOLITE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CELL CLONE; CELL CULTURE; CHO CELL; COMET ASSAY; CONCENTRATION RESPONSE; CONTROLLED STUDY; DNA STRAND BREAKAGE; GENE EXPRESSION; GENE MUTATION; GENETIC ENGINEERING; GENOTOXICITY; MUTAGENICITY; NONHUMAN; NUCLEIC ACID ANALYSIS; OXIDATION REDUCTION STATE;

ANILINE COMPOUNDS; ANIMALS; CELL SURVIVAL; CELLS, CULTURED; CHO CELLS; CRICETINAE; CRICETULUS; DNA ADDUCTS; DNA BREAKS, DOUBLE-STRANDED; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; MICE; MICROSOMES, LIVER; MUTAGENICITY TESTS; MUTAGENS; MUTATION; OXIDATION-REDUCTION; REACTIVE OXYGEN SPECIES;

EID: 84867807941     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfs229     Document Type: Article

References (51)

1. Adams, R., and Schowalter, K. A. (1952). Quinone imides. X. Addition of amines to p-quinonedibenzenesulfonimide. J. Am. Chem. Soc. 74, 2597-2602.
2. Albert, H. E. (1954). Some new amino alkylphenols. J. Am. Chem. Soc. 76, 4985-4988.
3. Beland, F. A., and Kadlubar, F. F. (1990). Metabolic activation and DNA adducts of aromatic amines and nitroaromatic hydrocarbons. In Handbook of Experimental Pharmacology. Chemical Carcinogenesis and Mutagenesis (C. S. Cooper and P. L. Grover, Eds.), Vol. 94/I, pp. 267-325. Springer-Verlag, Berlin.
4. Besaratinia, A., Bates, S. E., and Pfeifer, G. P. (2002). Mutational signature of the proximate bladder carcinogen N-hydroxy-4-acetylaminobiphenyl: Inconsistency with the p53 mutational spectrum in bladder cancer. Cancer Res. 62, 4331-4338.
5. Breimer, L. H. (1990). Molecular mechanisms of oxygen radical carcinogenesis and mutagenesis: The role of DNA base damage. Mol. Carcinog. 3, 1082-1086.
6. Brennan, R. J., and Schiestl, R. H. (1997). Aniline and its metabolites generate free radicals in yeast. Mutagenesis 12, 215-220.
7. Chen, T., Mittelstaedt, R. A., Beland, F. A., Heflich, R. H., Moore, M. M., and Parsons, B. L. (2005). 4-Aminobiphenyl induces liver DNA adducts in both neonatal and adult mice but induces liver mutations only in neonatal mice. Int. J. Cancer 117, 182-187.
8. Cui, L., Sun, H. L., Wishnok, J. S., Tannenbaum, S. R., and Skipper, P. L. (2007). Identification of adducts formed by reaction of N-acetoxy-3,5-dimethylaniline with DNA. Chem. Res. Toxicol. 20, 1730-1736.
9. Eyer, P. (1994). Reactions of oxidatively activated arylamines with thiols: Reaction mechanisms and biologic implications. An overview. Environ. Health Perspect. 102(Suppl. 6), 123-132.
10. Famulok, M., and Boche, G. (1989). Formation of N-(deoxyguanosin-8-yl)aniline in the in vitro reaction of N-acetoxyaniline with deoxyguanosine and DNA. Angew. Chem. Int. Ed. Engl. 28, 468-469.
11. Fishbein, J. C., and McClelland, R. A. (1987). Azide ion trapping of the intermediate in the Bamberger rearrangement. Lifetime of a free nitrenium ion in aqueous solution. J. Am. Chem. Soc. 109, 2824-2825.
12. Gan, J., Skipper, P. L., and Tannenbaum, S. R. (2001). Oxidation of 2,6-dimethylaniline by recombinant human cytochrome P450s and human liver microsomes. Chem. Res. Toxicol. 14, 672-677.
13. Gan, J., Skipper, P. L., Gago-Dominguez, M., Arakawa, K., Ross, R. K., Yu, M. C., and Tannenbaum, S. R. (2004). Alkylaniline-hemoglobin adducts and risk of non-smoking-related bladder cancer. J. Natl. Cancer Inst. 96, 1425-1431.
14. Gonçalves, L. L., Beland, F. A., and Marques, M. M. (2001). Synthesis, characterization, and comparative 32P-postlabeling efficiencies of 2,6-dimethylaniline-DNA adducts. Chem. Res. Toxicol. 14, 165-174.
15. Guliaev, A. B., Hang, B., and Singer, B. (2004). Structural insights by molecular dynamics simulations into specificity of the major human AP endonuclease toward the benzene-derived DNA adduct, pBQ-C. Nucleic Acids Res. 32, 2844-2852.
16. Hill, A. B., Jefferies, P. R., Quistad, G. B., and Casida, J. E. (1997). Dialkylquinoneimine metabolites of chloroacetanilide herbicides induce sister chromatid exchanges in cultured human lymphocytes. Mutat. Res. 395, 159-171.
17. Hill, B. A., Kleiner, H. E., Ryan, E. A., Dulik, D. M., Monks, T. J., and Lau, S. S. (1993). Identification of multi-S-substituted conjugates of hydroquinone by HPLC-coulometric electrode array analysis and mass spectrometry. Chem. Res. Toxicol. 6, 459-469.
18. IARC. (1972). 4-Aminobiphenyl. In IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, Vol. 1, pp. 74-79. International Agency for Research on Cancer, Lyon, France.
19. Irving, C. C., and Gutmann, H. R. (1961). Protein binding of model quinone imides. III. Preparation of Ne-(1-hydroxy-2-acetamido-4-fluorenyl)-DLlysine. J. Org. Chem. 26, 1859-1861.
20. Jakubowski, W., and Bartosz, G. (2000). 2,7-dichlorofluorescin oxidation and reactive oxygen species: What does it measure? Cell Biol. Int. 24, 757-760.
21. Jefferies, P. R., Quistad, G. B., and Casida, J. E. (1998). Dialkylquinonimines validated as in vivo metabolites of alachlor, acetochlor, and metolachlor herbicides in rats. Chem. Res. Toxicol. 11, 353-359.
22. Jeong, J. K., Wogan, G. N., Lau, S. S., and Monks, T. J. (1999). Quinolglutathione conjugate-induced mutation spectra in the supF gene replicated in human AD293 cells and bacterial MBL50 cells. Cancer Res. 59, 3641-3645.
23. Johansson, F., Allkvist, A., Erixon, K., Malmvärn, A., Nilsson, R., Bergman, A., Helleday, T., and Jenssen, D. (2004). Screening for genotoxicity using the DRAG assay: Investigation of halogenated environmental contaminants. Mutat. Res. 563, 35-47.
24. Jones, C. R., and Sabbioni, G. (2003). Identification of DNA adducts using HPLC/MS/MS following in vitro and in vivo experiments with arylamines and nitroarenes. Chem. Res. Toxicol. 16, 1251-1263.
25. Kadlubar, F. F. (1994). DNA adducts of carcinogenic aromatic amines. In DNA Adducts: Identification and Biological Significance. IARC Scientific Publications No. 125 (K. Hemminki, A. Dipple, D. E. G. Shuker, F. F. Kadlubar, D. Segerbäck, and H. Bartsch, Eds.), pp. 199-216. International Agency for Research on Cancer, Lyon, France.
26. Kamm, O. (1941). β-Phenylhydroxylamine. In Organic Syntheses, Collective Vol. 1, p. 445. Wiley, New York, NY.
27. Klos, C., Koob, M., Kramer, C., and Dekant, W. (1992). p-aminophenol nephrotoxicity: Biosynthesis of toxic glutathione conjugates. Toxicol. Appl. Pharmacol. 115, 98-106.
28. Lau, S. S., Monks, T. J., Everitt, J. I., Kleymenova, E., and Walker, C. L. (2001). Carcinogenicity of a nephrotoxic metabolite of the "nongenotoxic" carcinogen hydroquinone. Chem. Res. Toxicol. 14, 25-33.
29. Li, W. W., Heinze, J., and Haehnel, W. (2005). Site-specific binding of quinones to proteins through thiol addition and addition-elimination reactions. J. Am. Chem. Soc. 127, 6140-6141.
30. Marques, M. M., Mourato, L. L., Santos, M. A., and Beland, F. A. (1996). Synthesis, characterization, and conformational analysis of DNA adducts from methylated anilines present in tobacco smoke. Chem. Res. Toxicol. 9, 99-108.
31. Martínez-Cabot, A., Morató, A., and Messeguer, A. (2005). Synthesis and stability studies of the glutathione and N-acetylcysteine adducts of an iminoquinone reactive intermediate generated in the biotransformation of 3-(N-phenylamino)propane-1,2-diol: Implications for toxic oil syndrome. Chem. Res. Toxicol. 18, 1721-1728.
32. McCarthy, D. J., Waud, W. R., Struck, R. F., and Hill, D. L. (1985). Disposition and metabolism of aniline in Fischer 344 rats and C57BL/6 X C3H F1 mice. Cancer Res. 45, 174-180.
33. Meier, C., and Boche, G. (1990). N-Aryl-O-(α-aminoacyl)hydroxylamine: Modellreaktionen mit desoxyguanosin, guanosin und 5'-guanosinmonophosphat zur aktivierung monocyclischer aromatischer amine (z.B. phenacetin) zu ultimaten carcinogenen. Chem. Ber. 123, 1699-1705.
34. Neeley, W. L., and Essigmann, J. M. (2006). Mechanisms of formation, genotoxicity, and mutation of guanine oxidation products. Chem. Res. Toxicol. 19, 491-505.
35. Newcomb, T. G., and Loeb, L. A. (1998). Mechanisms of mutagenicity of oxidatively-modified bases. In Molecular Biology of Free Radicals in Human Diseases (O. I. Aruoma and B. Halliwell, Eds.), pp. 139-166. OICA International, London.
36. Novak, M., and Kennedy, S. A. (1995). Selective trapping of N-acetyl-N-(4-biphenylyl)nitrenium and N-acetyl-N-(2-fluorenyl)nitrenium ions by 2'-deoxyguanosine in aqueous solution. J. Am. Chem. Soc. 117, 574-575.
37. Novak, M., Kahley, M. J., Lin, J., Kennedy, S. A., and James, T. G. (1995). Involvement of free nitrenium ions, ion pairs, and preassociation trapping in the reactions of ester derivatives of N-arylhydroxylamines and N-arylhydroxamic acids in aqueous solution. J. Org. Chem. 60, 8294-8304.
38. Patel, S. K., Ma, N., Monks, T. J., and Lau, S. S. (2003). Changes in gene expression during chemical-induced nephrocarcinogenicity in the Eker rat. Mol. Carcinog. 38, 141-154.
39. Reid, T. M., and Loeb, L. A. (1986). Mutagenic specificity of oxygen radicals produced by human leukemia cells. Cancer Res. 52, 1082-1086.
40. Slaughter, D. E., and Hanzlik, R. P. (1991). Identification of epoxide- and quinone-derived bromobenzene adducts to protein sulfur nucleophiles. Chem. Res. Toxicol. 4, 349-359.
41. Son, O. S., Everett, D. W., and Fiala, E. S. (1980). Metabolism of o-[methyl-14C]toluidine in the F344 rat. Xenobiotica 10, 457-468.
42. Thilly, W. G. (1985). Dead cells don't form mutant colonies: A serious source of bias in mutation assays. Environ. Mutagen. 7, 255-258.
43. Tindall, K. R., and Stankowski, L. F., Jr. (1989). Molecular analysis of spontaneous mutations at the gpt locus in Chinese hamster ovary (AS52) cells. Mutat. Res. 220, 241-253.
44. Towndrow, K. M., Mertens, J. J., Jeong, J. K., Weber, T. J., Monks, T. J., and Lau, S. S. (2000). Stress- and growth-related gene expression are independent of chemical-induced prostaglandin E(2) synthesis in renal epithelial cells. Chem. Res. Toxicol. 13, 111-117.
45. Turesky, R. J., Lang, N. P., Butler, M. A., Teitel, C. H., and Kadlubar, F. F. (1991). Metabolic activation of carcinogenic heterocyclic aromatic amines by human liver and colon. Carcinogenesis 12, 1839-1845.
46. Wang, D., Kreutzer, D. A., and Essigmann, J. M. (1998). Mutagenicity and repair of oxidative DNA damage: Insights from studies using defined lesions. Mutat. Res. 400, 99-115.
47. Weber, T. J., Huang, Q., Monks, T. J., and Lau, S. S. (2001). Differential regulation of redox responsive transcription factors by the nephrocarcinogen 2,3,5-Tris(glutathion-S-yl)hydroquinone. Chem. Res. Toxicol. 14, 814-821.
48. Wood, D. K., Weingeist, D. M., Bhatia, S. N., and Engelward, B. P. (2010). Single cell trapping and DNA damage analysis using microwell arrays. Proc. Natl. Acad. Sci. U.S.A. 107, 10008-10013.
49. Wu, R. W., Panteleakos, F. N., and Felton, J. S. (2003). Development and characterization of CHO repair-proficient cell lines for comparative mutagenicity and metabolism of heterocyclic amines from cooked food. Environ. Mol. Mutagen. 41, 7-13.
50. Yang, M. Y., Lau, S. S., and Monks, T. J. (2005). 2,3,5-tris(Glutathion-S-yl)hydroquinone (TGHQ)-mediated apoptosis of human promyelocytic leukemia cells is preceded by mitochondrial cytochrome c release in the absence of a decrease in the mitochondrial membrane potential. Toxicol. Sci. 86, 92-100.
51. Yoon, H. S., Monks, T. J., Walker, C. L., and Lau, S. S. (2001). Transformation of kidney epithelial cells by a quinol thioether via inactivation of the tuberous sclerosis-2 tumor suppressor gene. Mol. Carcinog. 31, 37-45.