Cytochrome P450 activation of arylamines and heterocyclic amines

Annual Review of Pharmacology and Toxicology

Volumn 45, Issue , 2005, Pages 27-49

  Kim, Donghak ^a   Guengerich, F Peter ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

DNA adducts; Food pyrolysis; Mutations; N acetyl transferase; N hydroxy arylamines

Indexed keywords

AROMATIC AMINE; CYTOCHROME P450; CYTOCHROME P450 1A1; CYTOCHROME P450 1A2; CYTOCHROME P450 1B1; DAPSONE; DIHYDRALAZINE; HETEROCYCLIC AMINE; SULFAMETHOXAZOLE;

AMINATION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; BLOOD DYSCRASIA; CANCER RISK; CARCINOGENICITY; CONTROLLED STUDY; DRUG BINDING; DRUG CROSS REACTIVITY; ENZYME ACTIVATION; ENZYME SUBUNIT; FEVER; HEMOLYSIS; HEPATITIS; HUMAN; HYDROXYLATION; LYMPHADENOPATHY; NEPHRITIS; NONHUMAN; PREDICTION; PRIMATE; PRIORITY JOURNAL; PROTEIN EXPRESSION; RASH; RAT; REACTION ANALYSIS; REVIEW; SIDE EFFECT; TOXIC HEPATITIS;

AMINES; ANIMALS; ARYLAMINE N-ACETYLTRANSFERASE; CYTOCHROME P-450 ENZYME SYSTEM; ENZYME ACTIVATION; HETEROCYCLIC COMPOUNDS; HUMANS;

ANIMALIA; PRIMATES;

EID: 13844316753     PISSN: 03621642     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.pharmtox.45.120403.100010     Document Type: Review

References (167)

1. Radomski JL. 1979. The primary aromatic amines: their biological properties and structure-activity relationships. Annu. Rev. Pharmacol. 19:129-57
2. Garner RC, Martin CN, Clayson DB. 1984. Carcinogenic aromatic amines and related compounds. In Chemical Carcinogens, ed. CE Searle, 1:175-276. Washington, DC: Amer. Chem. Soc. 2nd ed.
3. Rehn L. 1895. Über Blasentumoren bei Fuchsinarbeitern. Archiv. Clin. Chirgurie 50:588-600
4. Heflich RH, Neft RE. 1994. Genetic toxicity of 2-acetylaminofluorene, 2-aminofluorene and some of their metabolites and model metabolites. Mutat. Res. 318:73-114
5. Verna L, Whysner J, Williams GM. 1996. 2-Acetylaminofluorene mechanistic data and risk assessment: DNA reactivity, enhanced cell proliferation and tumor initiation. Pharmacol. Ther. 71:83-105
6. Kriek E. 1974. Carcinogenesis by aromatic amines. Biochim. Biophys. Acta 355:177-203
7. Widmark EMP. 1939. Presence of cancer-producing substances in roasted food. Nature 143:984
8. Murkovic M. 2004. Formation of heterocyclic amines in model systems. J. Chromatog. B 802:3-10
9. Sugimura T, Nagao M, Kawachi T. 1977. Mutagens-carcinogens in foods, with special reference to highly mutagenic pyrolytic products in broiled foods. In Origins of Human Cancer, ed. HH Hiatt, JD Watson, JA Winsten, pp. 1561-77. Cold Spring Habor: Cold Spring Harbor Lab. Press
10. Nagao M, Honda M, Seino Y, Yahagi T, Sugimura T. 1977. Mutagenicities of smoke condensates and the charred surface of fish and meat. Cancer Lett. 2:221-26
11. Sugimura T. 1995. History, present and future, of heterocyclic amines, cooked food mutagens. In Heterocyclic Amines and Human Cancer, ed. RH Adamson, J-Å Gustafsson, N Ito, M Nagao, K Wakabayashi, Y Yamazoe, 23:214-31. Princeton, NJ: Princeton Sci. Publ.
12. Nagao M, Sugimura T, Matsushima T. 1978. Environmental mutagens and carcinogens. Annu. Rev. Genet. 12:117-59
13. Sugimura T. 1978. Let's be scientific about the problem of mutagens in cooked food. Mutat. Res. 55:149-52
14. Sugimura T. 1986. Studies on environmental chemical carcinogenesis in Japan. Science 233:312-18
15. Jägerstad M, Grivas S, Olsson K, Laser Reutersward A, Negishi C, et al. 1986. Formation of food mutagens via Maillard reactions. Prog. Clin. Biol. Res. 206:155-67
16. Hatch FT, Felton JS. 1986. Toxicologic strategy for mutagens formed in foods during cooking: status and needs. Prog. Clin. Biol. Res. 206:109-31
17. Jägerstad M, Reutersward AL, Oeste R, Dahlqvist A, Grivas S, et al. 1983. Creatinine and Maillard reaction products as precursors of mutagenic compounds formed fried beefs. In The Maillard Reaction in Foods and Nutrition, ed. GR Waller, MS Feather, pp. 507-19. Washington, DC: Amer. Chem. Soc.
18. Grivas S, Nyhammar T, Olsson K, Jägerstad M. 1985. Formation of a new mutagenic DiMeIQx compound in a model system by heating creatinine, alanine and fructose. Mutat. Res. 151:177-83
19. Nyhammar T, Grivas S, Olsson K, Jägerstad M. 1986. Formation of 4,8-DiMeIQx from the model system fructose, alanine and creatinine. Comparison with the isomeric 5,8-DiMeIQx. Mutat. Res. 174:5-9
20. Eisenbrand G, Tang W. 1993. Food-borne heterocyclic amines. Chemistry, formation, occurrence and biological activities. A literature review. Toxicology 84:1-82
21. Sugimura T. 1986. Past, present, and future of mutagens in cooked foods. Environ. Health Perspect. 67:5-10
22. Felton JS, Jagerstad M, Knize MG, Skog K, Wakabayashi K. 2000. Contents in foods, beverages and tobacco. In Food Borne Carcinogens Heterocyclic Amines, ed. M Nagao, T Sugimura, pp. 31-71. West Sussex, UK: Wiley
23. Turesky RJ. 2002. Heterocyclic aromatic amine metabolism, DNA adduct formation, mutagenesis, and carcinogenesis. Drug Metab. Rev. 34:625-50
24. Shimada T, Guengerich FP. 1991. Activation of amino-a-carboline, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, and a copper phthalocyanine cellulose extract of cigarette smoke condensate by cytochrome P-450 enzymes in rat and human liver microsomes. Cancer Res. 51:5284-91
25. Manabe S, Tohyama K, Wada O, Aramaki T. 1991. Detection of a carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), in cigarette smoke condensate. Carcinogenesis 12:1945-47
26. Svensson CK. 2003. Do arylhydroxylamine metabolites mediate idiosyncratic reactions associated with sulfonamides? Chem. Res. Toxicol. 16:1035-43
27. Naisbitt DJ. 2004. Drug hypersensitivity reactions in skin: understanding mechanisms and the development of diagnostic and predictive tests. Toxicology 194:179-96
28. Gorlewska-Roberts K, Green B, Fares M, Ambrosone CB, Kadlubar FF. 2002. Carcinogen-DNA adducts in human breast epithelial cells. Environ. Mol. Mutagen. 39:184-92
29. Turesky RJ, Freeman JP, Holland RD, Nestorick DM, Miller DW, et al. 2003. Identification of aminobiphenyl derivatives in commercial hair dyes. Chem. Res. Toxicol. 16:1162-73
30. Gago-Dominguez M, Bell DA, Watson MA, Yuan JM, Castelao JE, et al. 2003. Permanent hair dyes and bladder cancer: risk modification by cytochrome P4501A2 and N-acetyltransferases 1 and 2. Carcinogenesis 24:483-89
31. Kadlubar FF, Hammons GJ. 1987. The role of cytochrome P-450 in the metabolism of chemical carcinogens. In Mammalian Cytochromes P-450, ed. FP Guengerich, 2:81-130. Boca Raton, FL: CRC Press
32. Frederick CB, Mays JB, Ziegler DM, Guengerich FP, Kadlubar FF. 1982. Cytochrome P-450 and flavin-containing monooxygenase-catalyzed formation of the carcinogen N-hydroxy-2-aminofluorene, and its covalent binding to nuclear DNA. Cancer Res. 42:2671-77
33. Hammons GJ, Guengerich FP, Weis CC, Beland FA, Kadlubar FF. 1985. Metabolic oxidation of carcinogenic arylamines by rat, dog, and human hepatic microsomes and by purified flavin-containing and cytochrome P-450 monooxygenases. Cancer Res. 45:3578-85
34. Yamazoe Y, Miller DW, Weis CC, Dooley KL, Zenser TV, et al. 1985. DNA adducts formed by ring-oxidation of the carcinogen 2-naphthylamine with prostaglandin H synthase in vitro and in the dog urothelium in vivo. Carcinogenesis 6:1379-87
35. Yamazoe Y, Zenser TV, Miller DW, Kadlubar FF. 1988. Mechanism of formation and structural characterization of DNA adducts derived from peroxidative activation of benzidine. Carcinogenesis 9:1635-41
36. Butler MA, Guengerich FP, Kadlubar FF. 1989. Metabolic oxidation of the carcinogens 4-aminobiphenyl and 4,4′-methylene-bis(2-chloroaniline) by human hepatic microsomes and by purified rat hepatic cytochrome P-450 monooxygenases. Cancer Res. 49:25-31
37. PA (P-450IA2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines. Proc. Natl. Acad. Sci. USA 86: 7696-700
38. Wallin H, Mikalsen A, Guengerich FP, Ingelman-Sundberg M, Solberg KE, et al. 1990. Different rates of metabolic activation and detoxication of the food mutagen 2-amino-l-methyl-6-phenylimidazo(4,5-f)pyridine by different cytochrome P-450 enzymes. Carcinogenesis 11:489-92
39. Seto Y, Guengerich FP. 1993. Partitioning between N-dealkylation and N-oxygenation in the oxidation of N,N-dialkylarylamines catalyzed by cytochrome P450 2B1. J. Biol. Chem. 268:9986-97
40. Kato R. 1986. Metabolic activation of mutagenic heterocyclic aromatic amines from protein pyrolysates. CRC Crit. Rev. Toxicol. 16:307-48
41. Kato R, Kamataki T, Saito K, Shinohara A. 1986. Acetyl-CoA dependent O-acetylation of N-hydroxyarylamines in bacterial and mammalian cells-the significance for mutagenesis and carcinogenesis. In Genetic Toxicology of Environmental Chemicals, Part A: Basic Principles and Mechanisms of Action, pp. 507-14. New York: Alan R Liss
42. Chou HC, Lang NP, Kadlubar FF. 1995. Metabolic activation of the N-hydroxy derivative of the carcinogen 4-aminobiphenyl by human tissue sulfotransferases. Carcinogenesis 16:413-17
43. Schut HAJ, Snyderwine EG. 1999. DNA adducts of heterocyclic amine food mutagens: implications for mutagenesis and carcinogenesis. Carcinogenesis 20:353-68
44. Snyderwine EG, Wirth PJ, Roller PP, Adamson RH, Sato S, et al. 1988. Mutagenicity and in vitro covalent DNA binding of 2-hydroxyamino-3-methyl- imidazolo[4,5-f]quinoline. Carcinogenesis 9:411-18
45. 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. 272:183-92
46. 32P-Postlabeling analysis of IQ, MeIQx and PhIP adducts formed in vitro in DNA and polynucleotides and found in vivo in hepatic DNA from IQ-, MeIQx- and PhIP-treated monkeys. Carcinogenesis 14:1389-95
47. 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. 334:145-56
48. Oda Y, Aryal P, Terashita T, Gillam EMJ, Guengerich FP, et al. 2001. Metabolic activation of heterocyclic amines and other procarcinogens in Salmonella typhimurium umu tester strains expressing human cytochrome P450 1A1, 1A2, 1B1, 2C9, 2D6, 2E1, and 3A4 and human NADPH-P450 reductase and bacterial O-acetyltransferase. Mutat. Res. 492:81-90
49. Miller JA, Surh YJ. 1994. Sulfonation in chemical carcinogenesis. In Handbook of Experimental Pharmacology. Vol. 112: Conjugation-Deconjugation Reactions in Drug Metabolism and Toxicity, ed. FC Kauffman, pp. 429-57. Berlin: Springer-Verlag
50. 2 atoms of guanine and at the N6 atom of adenine. Carcinogenesis 1:139-50
51. Beland FA, Kadlubar FF. 1990. Metabolic activation and DNA adducts of aromatic amines and nitroaromatic hydrocarbons. In Handbook of Experimental Pathology. Carcinogenesis and Mutagenesis, ed. CS Cooper, PL Grover, Vol. 94/I, pp. 267-325. Heidelberg: Springer-Verlag
52. Wild D, Dirr A, Fasshauer I, Henschler D. 1989. Photolysis of arylazides and generation of highly electrophilic DNA-binding and mutagenic intermediates. Carcinogenesis 10:335-41
53. Guengerich FP. 2002. N-Hydroxyarylamines. Drug Metab. Rev. 34:607-23
54. Novak M, Xu LL, Wolf RA. 1998. Nitrenium ions from food-derived heterocyclic arylamine mutagens. J. Am. Chem. Soc. 120:1643-44
55. Humphreys WG, Kadlubar FF, Guengerich FP. 1992. Mechanism of C8 alkylation of guanyl residues by activated arylamines: evidence for a role of initial attack at the N7 atom. Proc. Natl. Acad. Sci. USA 89:8278-82
56. 7-aminoguanosine and derivatives. Chem. Res. Toxicol. 12:906-16
57. Hashimoto Y, Shudo K, Okamoto T. 1982. Modification of nucleic acids with mutacarcinogenic heteroaromatic amines in vivo. Identification of modified bases in DNA extracted from rats injected with 3-amino-1-methyl-5H-pyrido[4,3-b] indole and 2-amino-6-methyldipyrido[1,2-a3:3′, 2′-d]imidazole. Mutat. Res. 105:9-13
58. Snyderwine EG, Roller PP, Adamson RH, Sato S, Thorgeirsson SS. 1988. Reaction of N-hydroxylamine and N-acetoxy derivatives of 2-amino-3- methylimidazolo[4,5-f]quinoline with DNA. Synthesis and identification of N-(deoxyguanosin-8-yl)-IQ. Carcinogenesis 9:1061-65
59. 2 atoms of guanine. Chem. Res. Toxicol. 5:479-90
60. 2-(2′-deoxyguanosin-8-yl)PhIP. Carcinogenesis 13:629-35
61. 32P-postlabeling method, in the liver of rats fed MeIQx. Carcinogenesis 14:2165-70
62. Tada A, Ochiai M, Wakabayashi K, Nukaya H, Sugimura T, et al. 1994. Identification of N-(deoxyguanosin-8-yl)-2-amino-3,4-dimethylimidazo[4,5-f] quinoline (dG-C8-MeIQ) as a major adduct formed by MeIQ with nucleotides in vitro with DNA in vivo. Carcinogenesis 15:1275-78
63. 2-(2′-deoxyguanosin-8-yl)-4,8-Di-MeIQx adduct. Carcinogenesis 15:2553-58
64. Shibutani S, Fernandes A, Suzuki N, Zhou L, Johnson F, et al. 1999. Mutagenesis of the N-(deoxyguanosin-8-yl)-2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine DNA adduct in mammalian cells. Sequence context effects. J. Biol. Chem. 274:27433-38
65. Wang Z, Rizzo CJ. 2001. Synthesis of the C8-deoxyguanosine adduct of the food mutagen IQ. Org. Lett. 3:565-68
66. 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. USA 70:2281-85
67. Ames BN, Kammen HO, Yamasaki E. 1975. Hair dyes are mutagenic: identification of a variety of mutagenic ingredients. Proc. Natl. Acad. Sci. USA 72:2423-27
68. 1-450. Proc. Natl. Acad. Sci. USA 76: 5929-33
69. Fuscoe JC, Wu R, Shen NH, Healy SK, Felton JS. 1988. Base-change analysis of revertants of the hisD3052 allele in Salmonella typhimurium. Mutat. Res. 201:241-51
70. Sugimura T. 1997. Overview of carcinogenic heterocyclic amines. Mutat. Res. 376:211-19
71. Kosakarn P, Halliday JA, Glickman BW, Josephy PD. 1993. Mutational specificity of 2-nitro-3,4-dimethylimidazo[4,5-f] quinoline in the lacI gene of Escherichia coli. Carcinogenesis 14:511-17
72. Watanabe M, Ohta T. 1993. Analysis of mutational specificity induced by heterocylic amines in the lacZ gene of Escherichia coli. Carcinogenesis 14:1149-53
73. Josephy PD, DeBruin LS, Lord HL, Oak J, Evans DH, et al. 1995. Bioactivation of aromatic amines by recombinant human cytochrome P450 1A2 expressed in bacteria: a substitute for mammalian tissue preparations in mutagenicity testing. Cancer Res. 55:799-802
74. Josephy PD, Evans DH, Parikh A, Guengerich FP. 1998. Metabolic activation of aromatic amine mutagens by simultaneous expression of human cytochrome P450 1A2, NADPH-cytochrome P450 reductase, and N-acetyltransferase in Escherichia coli. Chem. Res. Toxicol. 11:70-74
75. Constable A, Varga N, Josephy PD, Guy P, Turesky RJ. 1999. Evaluation of Escherichia coli DJ4309 expressing human P450 1A2 in mutagenicity testing of complex food mixtures. Mutat. Res. 442:79-87
76. Josephy PD. 2000. The Escherichia coli lacZ reversion mutagenicity assay. Mutat. Res. 455:71-80
77. Marwood TM, Meyer D, Josephy PD. 1995. Escherichia coli lacZ strains engineered for detection of frameshift mutations induced by aromatic amines and nitroaromatic compounds. Carcinogenesis 16:2037-43
78. Watanabe M, Nohmi T, Ishidate M Jr. 1987. New tester strains of Salmonella typhimurium highly sensitive to mutagenic nitroarenes. Biochem. Biophys. Res. Commun. 147:974-79
79. Suzuki A, Kushida H, Iwata H, Watanabe M, Nohmi T, et al. 1998. Establishment of a Salmonella tester strain highly sensitive to mutagenic heterocyclic amines. Cancer Res. 58:1833-38
80. Fujita K-I, Kamataki T. 2002. Genetically engineered bacterial cells co-expressing human cytochrome P450 with NADPH-cytochrome P450 reductase: prediction of metabolism and toxicity of drugs in humans. Drug Metab. Pharmacokin. 17:1-22
81. Parikh A, Josephy PD, Guengerich FP. 1999. Selection and characterization of human cytochrome P450 1A2 mutants with altered catalytic properties. Biochemistry 38:5283-89
82. Josephy PD, Bibeau KL, Evans DH. 2000. Activation of MeIQ (2-amino-3,4-dimethylimidazo-[4,5-f]quinoline) by sequence variants of recombinant human cytochrome P450 1A2. Environ. Mol. Mutagen. 35:328-35
83. Kim D, Guengerich FP. 2004. Selection of human cytochrome P450 1A2 mutants with selectivity enhanced catalytic activity for heterocyclic amine N-hydroxylation. Biochemistry 43:981-88
84. Zhou H, Josephy PD, Kim D, Guengerich FP. 2004. Functional characterization of four allelic variants of human cytochrome P450 1A2. Arch. Biochem. Biophys. 422:23-30
85. Chun Y-J, Kim S, Kim D, Lee S-K, Guengerich FP. 2001. A new selective and potent inhibitor of human cytochrome P450 1B1 and its application to antimutagenesis. Cancer Res. 61:8164-70
86. Langouët S, Furge LL, Kerriguy N, Nakamura K, Guillouzo A, et al. 2000. Inhibition of human cytochrome P450 enzymes by 1,2-dithiole-3-thione, oltipraz and its derivatives, and sulforaphane. Chem. Res. Toxicol. 13:245-52
87. Poirier MC, Beland FA. 1992. DNA adduct measurements and tumor incidence during chronic carcinogen exposure in animal models: implications for DNA adduct-based human cancer risk assessment. Chem. Res. Toxicol. 5:749-55
88. Hemminki K. 1993. DNA adducts, mutations and cancer. Carcinogenesis 14:2007-12
89. Nagao M, Ushijima T, Toyota M, Inoue R, Sugimura T. 1997. Genetic changes induced by heterocyclic amines. Mutat. Res. 376:161-67
90. Fujimoto Y, Hampton LL, Snyderwine EG, Nagao M, Sugimura T, et al. 1994. p53 gene mutation in hepatocellular carcinoma induced by 2-amino-3- methylimidazo[4,5-f]quinoline in nonhuman primates. Jpn. J. Cancer Res. 85:506-9
91. Okonogi H, Stuart GR, Okochi E, Ushijima T, Sugimura T, et al. 1997. Effects of gender and species on spectra of mutation induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in the lacI, transgene. Mutat. Res. 395:93-99
92. Randerath K, Randerath E, Agrawal HP, Gupta RC, Schurdak ME, et al. 1985. Postlabeling methods for carcinogen-DNA adduct analysis. Environ. Health Perspect. 62:57-65
93. Turesky RJ, Vouros P. 2004. Formation and analysis of heterocyclic aromatic amine-DNA adducts in vitro and in vivo. J. Chromatog. B 803:155-66
94. Turesky RJ, Markovic J, Bracco-Hammer I, Fay LB. 1991. The effect of dose and cytochrome P450 induction on the metabolism and disposition of the food-borne carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in the rat. Carcinogenesis 12:1847-55
95. Turesky RJ, Constable A, Richoz J, Varga N, Markovic J, et al. 1998. Activation of heterocyclic aromatic amines by rat and human liver microsomes and by purified rat and human cytochrome P450 1A2. Chem. Res. Toxicol. 11:925-36
96. Kadlubar FF, Miller JA, Miller EC. 1976. Microsomal N-oxidation of the hepatocarcinogen N-methyl-4-aminoazobenzene and the reactivity of N-hydroxy-N-methyl-4-aminoazobenzene. Cancer Res. 36:1196-206
97. Hueper WC, Wiley FH, Wolfe HD. 1938. Experimental production of bladder tumors in dogs by administration of beta-naphthylamine. J. Indust. Hygiene Toxicol. 20:46-84
98. Sugimura T. 1985. Carcinogenicity of mutagenic heterocyclic amines formed during the cooking process. Mutat. Res. 150:33-41
99. Kato T, Ohgaki H, Hasegawa H, Sato S, Takayama S, et al. 1988. Carcinogenicity in rats of a mutagenic compound, 2-amino-3,8-dimethylimidazo[4, 5-f]quinoxaline. Carcinogenesis 9:71-73
100. Nagao M, Sugimura T. 1993. Carcinogenic factors in food with relevance to colon cancer development. Mutat. Res. 290:43-51
101. Mueller GC, Miller JA. 1948. The metabolism of 4-dimethylaminoazobenzene by rat liver homogenates. J. Biol. Chem. 176:535-44
102. Cramer JW, Miller JA, Miller EC. 1960. N-Hydroxylation: a new metabolic reaction observed in the rat with the carcinogen 2-acetylaminofluorene. J. Biol. Chem. 235:885-88
103. Thorgeirsson SS, Jollow DJ, Sasame HA, Green I, Mitchell JR. 1973. The role of cytochrome P-450 in N-hydroxylation of 2-acetylaminofluorene. Mol. Pharmacol. 9:398-404
104. Felton JS, Nebert DW, Thorgeirsson SS. 1976. Genetic differences in 2-acetylaminofluorene mutagenicity in vitro associated with mouse hepatic arylhydrocarbon hydroxylase activity induced by polycyclic aromatic compounds. Mol. Pharmacol. 12:225-33
105. Dybing E, von Bahr C, Aune T, Glaumann H, Levitt DS, et al. 1979. In vitro metabolism and activation of carcinogenic aromatic amines by subcellular fractions of human liver. Cancer Res. 39:4206-11
106. McManus ME, Minchin RF, Sanderson N, Schwartz D, Johnson EF, et al. 1984. Metabolic processing of 2-acetyl-aminofluorene by microsomes and six highly purified cytochrome P-450 forms from rabbit liver. Carcinogenesis 5:1717-23
107. Wang PP, Beaune P, Kaminsky LS, Dannan GA, Kadlubar FF, et al. 1983. Purification and characterization of six cytochrome P-450 isozymes from human liver microsomes. Biochemistry 22:5375-83
108. Distlerath LM, Reilly PEB, Martin MV, Davis GG, Wilkinson GR, et al. 1985. Purification and characterization of the human liver cytochromes P-450 involved in debrisoquine 4-hydroxylation and phenacetin O-deethylation, two prototypes for genetic polymorphism in oxidative drug metabolism. J. Biol. Chem. 260:9057-67
109. Shimada T, Iwasaki M, Martin MV, Guengerich FP. 1989. Human liver microsomal cytochrome P-450 enzymes involved in the bioactivation of procarcinogens detected by umu gene response in Salmonella typhimurium TA1535/pSK1002. Cancer Res. 49:3218-28
110. Pantuck EJ, Hsiao K-C, Maggio A, Nakamura K, Kuntzman R, et al. 1974. Effect of cigarette smoking on phenacetin metabolism. Clin. Pharmacol. Therapeut. 15:9-17
111. Butler MA, Lang NP, Young JF, Caporaso NE, Vineis P, et al. 1992. Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites. Pharmacogenetics 2:116-27
112. Shimada T, Guengerich FP. 1990. Inactivation of 1,3-, 1,6-, and 1,8-dinitropyrene by human and rat microsomes. Cancer Res. 50:2036-43
113. Guengerich FP, Shimada T. 1991. Oxidation of toxic and carcinogenic chemicals by human cytochrome P-450 enzymes. Chem. Res. Toxicol. 4:391-407
114. Yun C-H, Shimada T, Guengerich FP. 1992. Contributions of human liver cytochrome P-450 enzymes to the N-oxidation of 4,4′-methylene-bis(2- chloroaniline). Carcinogenesis 13:217-22
115. Shimada T, Yamazaki H, Guengerich FP. 1992. Roles of rat pulmonary rnicrosomal cytochrome P-450 enzymes involved in the activation of procarcinogens. Mutat. Res. 283:233-41
116. Shimada T, Gillam EMJ, Sandhu P, Guo Z, Tukey RH, et al. 1994. Activation of procarcinogens by human cytochrome P450 enzymes expressed in Escherichia coli. Simplified bacterial systems for genotoxicity assays. Carcinogenesis 15:2523-29
117. Boobis AR, Lynch AM, Murray S, de la Toore R, Solans A, et al. 1994. CYP1A2-catalyzed conversion of dietary heterocyclic amines to their proximate carcinogens is their major route of metabolism in humans. Cancer Res. 54:89-94
118. Shimada T, Hayes CL, Yamazaki H, Amin S, Hecht SS, et al. 1996. Activation of chemically diverse procarcinogens by human cytochrome P450 1B1. Cancer Res. 56:2979-84
119. Josephy PD, Batty SM, Boverhof DR. 2001. Recombinant human P450 forms 1A1, 1A2, and 1B1 catalyze the bioactivation of heterocyclic amine mutagens in Escherichia coli lacZ strains. Environ. Mol. Mutagen. 38:12-18
120. Kitada M, Taneda M, Itahashi K, Kamataki T. 1991. Four forms of cytochrome P-450 in human fetal liver: purification and their capacity to activate promutagens. Jpn. J. Cancer Res. 82:426-32
121. Ayesh R, Idle JR, Ritchie JC, Crothers MJ, Hetzel MR. 1984. Metabolic oxidation phenotypes as markers for susceptibility to lung cancer. Nature 312:169-70
122. Wolff T, Distlerath LM, Worthington MT, Groopman JD, Hammons GJ, et al. 1985. Substrate specificity of human liver cytochrome P-450 debrisoquine 4-hydroxylase probed using immunochemical inhibition and chemical modeling. Cancer Res. 45:2116-22
123. Langouët S, Paehler A, Welti DH, Kerriguy N, Guillouzo A, et al. 2002. Differential metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in rat and human hepatocytes. Carcinogenesis 23:115-22
124. Richardson HL, Stier AR, Borsos-Nachtnebel E. 1952. Liver tumor inhibition and adrenal histologic responses in rats to which 3′-methyl-4-dimethylaminoazobenzene and 20-methylcholanthrene were simultaneously administered. Cancer Res. 12:356-61
125. Snyderwine EG, Yu M, Schut HA, Knight-Jones L, Kimura S. 2002. Effect of CYP1A2 deficiency on heterocyclic amine DNA adduct levels in mice. Food Chem. Toxicol. 40:1529-33
126. Kimura S, Kawabe M, Yu A, Morishima H, Fernandez-Salguero P, et al. 2003. Carcinogenesis of the food mutagen PhIP in mice is independent of CYP1A2. Carcinogenesis 24:583-87
127. Turesky RJ, Constable A, Richoz J, Vargu N, Markovic J, et al. 1998. Differences in activation of heterocyclic aromatic amines by rat and human liver microsomes and by rat and human cytochromes P450 1A2. Chem. Res. Toxicol. 11:925-36
128. Turesky RJ, Constable A, Fay LB, Guengerich FP. 1999. Interspecies differences in metabolism of heterocyclic aromatic amines by rat and human P450 1A2. Cancer Lett. 143:109-12
129. Guengerich FP. 1997. Comparisons of catalytic selectivity of cytochrome P450 sub-family members from different species. Chem Biol. Interact. 106:161-82
130. Langouët S, Welti DH, Kerriguy N, Fay LB, Markovic J, et al. 2001. Metabolism of 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline in human hepatocytes: 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline-8-carboxylic acid is a major detoxication pathway catalyzed by cytochrome P450 1A2. Chem. Res. Toxicol. 14:211-21
131. 8 and N-oxidation of 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline by human and rat liver microsomes and cytochromes P450 1A2. Chem. Res. Toxicol. 14:901-11
132. Adamson RH, Snyderwine EG, Thorgeirsson UP, Schut HA, Turesky RJ, et al. 1990. Metabolic processing and carcinogenicity of heterocyclic amines in nonhuman primates. In Heterocyclic Amines and Human Cancer, ed. RH Adamson, J-Å, Gustafsson, N Ito, M Nagao, K Wakabayashi, 21:289-301. Princeton, NJ: Princeton Sci. Publ.
133. Snyderwine EG, Turesky RJ, Turteltaub KW, Davis CD, Sadrieh N, et al. 1997. Metabolism of food-derived heterocyclic amines in nonhuman primates. Mutat. Res. 376:203-10
134. Adamson RH. 2000. Carcinogenicity in H animals and specific organs. In Food Borne Carcinogens Heterocyclic Amines, ed. M Nagao, T Sugimura, pp. 229-40. West Sussex, UK: Wiley H
135. Wild D, Degen GH. 1987. Prostaglandin H synthase-dependent mutagenic activation of heterocyclic aromatic amines of the IQ-type. Carcinogenesis 8:541-45.
136. Wolz E, Pfau W, Degen GH. 2000. Bioactivation of the food mutagen 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) by prostaglandin-H synthase and by monooxygenases: DNA adduct analysis. Food Chem. Toxicol. 38:513-22
137. Degen GH, Gerber MM, Obrecht-Pflumio S, Dirheimer G. 1997. Induction of micronuclei with ochratoxin A in ovine seminal vesicle cell cultures. Arch. Toxicol. 71:365-71
138. Guengerich FP. 2001. Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem. Res. Toxicol. 14:611-50
139. Ortiz de Montellano PR. 1995. Oxygen activation and reactivity. In Cytochrome P450: Structure, Mechanism, and Biochemistry, ed. PR Ortiz de Montellano, pp. 245-303. New York: Plenum Press
140. Kim D, Kadlubar FF, Teitel CH, Guengerich FP. 2004. Formation and reduction of aryl and heterocyclic nitroso compounds and significance in the flux of hydroxylamines. Chem. Res. Toxicol. 17:529-36
141. Morrison LD, Eling TE, Josephy PD. 1993. Prostaglandin H synthase-dependent formation of the direct-acting mutagen 2-nitro-3- methylimidazo[4,5-f]quinoline (nitro-IQ) from IQ. Mutat Res. 302:45-52
142. Wolz E, Wild D, Degen GH. 1995. Prostaglandin-H synthase mediated metabolism and mutagenic activation of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Arch. Toxicol. 69:171-79
143. El-Bayoumy K. 1992. Environmental carcinogens that may be involved in human breast cancer etiology. Chem. Res. Toxicol. 5:585-90
144. Klehr H, Eyer P, Schäfer W. 1987. Formation of 4-ethoxy-4′- nitrosodiphenylamine in the reaction of the phenacetin metabolite 4-nitrosophenetol with glutathione. Biol. Chem. Hoppe-Seyler 368:895-902
145. Eyer P. 1988. Detoxication of N-oxygenated arylamines in erythrocytes. An overview. Xenobiotica 18:1327-33
146. Mandell GL, Sande MA. 1985. Anti-microbial agents: sulfonamides, trimethoprim-sulfamethoxazole and agents for urinary tract infections. In The Pharmacological Basis of Therapeutics, ed. AG Gillam, LS Goodman, TW Rall, R Marud, pp. 1095-114. New York: Macmillan
147. Cribb AE, Spielberg SP, Griffin GP. 1995. N4-hydroxylation of sulfamethoxazole by cytochrome P450 of the cytochrome P4502C subfamily and reduction of sulfamethoxazole hydroxylamine in human and rat hepatic microsomes. Drug Metab. Dispos. 23:406-14
148. Naisbitt DJ, Hough SJ, Gill HJ, Pirmohamed M, Kitteringham NR, et al. 1999. Cellular disposition of sulphamethoxazole and its metabolites: implications for hypersensitivity. Br. J. Pharmacol. 126:1393-407
149. Cribb AE, Nuss CE, Alberts DW, Lamphere DB, Grant DM, et al. 1996. Covalent binding of sulfamethoxazole reactive metabolites to human and rat liver subcellular fractions assessed by immunochemical detection. Chem. Res. Toxicol. 9:500-7
150. Carr A, Tindall B, Penny R, Cooper DA. 1993. In vitro cytotoxicity as a marker of hypersensitivity to sulphamethoxazole in patients with HTV. Clin. Exp. Immunol. 94:21-25
151. Meekins CV, Sullivan TJ, Gruchalla RS. 1994. Immunochemical analysis of sulfonamide drug allergy: identification of sulfamethoxazole-substituted human serum proteins. J. Allergy Clin. Immunol. 94:1017-24
152. Rieder MJ, Krause R, Bird IA. 1995. Time-course of toxicity of reactive sulfonamide metabolites. Toxicology 95:141-46
153. Bourdi M, Larrey D, Nataf J, Berunau J, Pessayre D, et al. 1990. A new anti-liver endoplasmic reticulum antibody directed against human cytochrome P-450 1A2: a specific marker of dihydralazine-induced hepatitis. J. Clin. Invest. 85:1967-73
154. Reilly TP, Woster PM, Svensson CK. 1999. Methemoglobin formation by hydroxylamine metabolites of sulfamethoxazole and dapsone: implications for differences in adverse drug reactions. J. Pharmacol. Exp. Ther. 288:951-59
155. Fleming CM, Branch RA, Wilkinson GR, Guengerich FP. 1992. Human liver microsomal N-hydroxylation of dapsone by cytochrome P-450 3A4. Mol. Pharmacol. 41:975-80
156. Gill HJ, Tingle MD, Park BK. 1995. N-Hydroxylation of dapsone by multiple enzymes of cytochrome P450: implications for inhibition of haemotoxicity. Br. J. Clin. Pharmacol. 40:531-38
157. Mitra AK, Thummel KE, Kalhorn TF, Kharasch ED, Unadkat JD, et al. 1995. Metabolism of dapsone to its hydroxylamine by CYP2E1 in vitro and in vivo. Clin. Pharmacol. Ther. 58:556-66
158. Winter HR, Wang Y, Unadkat JD. 2000. CYP2C8/9 mediate dapsone N-hydroxylation at clinical concentrations of dapsone. Drug Metab. Dispos. 28:865-68
159. Skog KI, Johansson MA, Jägerstad MI. 1998. Carcinogenic heterocyclic amines in model systems and cooked foods: a review on formation, occurrence and intake. Food Chem. Toxicol. 36:879-96
160. Talaska G, Al-Juburi AZSS, Kadlubar FF. 1991. Smoking related carcinogen-DNA adducts in biopsy samples of human urinary bladder: identification of N-(deoxyguanosin-8-yl)-4-aminobiphenyl as a major adduct. Proc. Natl. Acad. Sci. USA 88:5350-54
161. Lin D, Lay JO Jr, Bryant MS, Malaveille C, Friesen M, et al. 1994. Analysis of 4-aminobiphenyl-DNA adducts in human urinary bladder and lung by alkaline hydrolysis and negative ion gas chromatography-mass spectrometry. Environ. Health Perspect. 102 (Suppl. 6):11-16
162. 32P-postlabeling, and GC/MS detection of 4-aminobiphenyl-DNA adducts in human peripheral lung in relation to metabolic activation pathways involving pulmonary N-oxidation, conjugation, and peroxidation. Mutat. Res. 378:97-112
163. Thompson PA, Seyedi F, Lang NP, MacLeod SL, Wogan GN, et al. 1999. Comparison of DNA adduct levels associated with exogenous and endogenous exposures in human pancreas in relation to metabolic genotype. Mutat. Res. 424:263-74
164. 32P-postlabeling. Chem. Res. Toxicol. 7:733-39
165. 2-(deoxyguanosin-8-yl)-2-amino-3, 8-dimethylimidazo[4,5- f]quinoxaline (d G-C8-MeIQx) in human tissues. Carcinogenesis 17:1029-34
166. Zhu J, Chang P, Bondy ML, Sahin AA, Singletary SE, et al. 2003. Detection of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine-DNA adducts in normal breast tissues and risk of breast cancer. Cancer Epidemiol. Biomarkers Prev. 12:830-37
167. Lang NP, Butler MA, Massengill J, Lawson M, Stotts RC, et al. 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. 3:675-82