The application of hepatic P450 reductase null gpt delta mice in studying the role of hepatic P450 in genotoxic carcinogen 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone-induced mutagenesis

Archives of Toxicology

Volumn 86, Issue 11, 2012, Pages 1753-1761

  Luan, Yang ^a   Xing, Guozhen ^a   Qi, Xinming ^a   Wu, Mengjun ^a,b   Li, Chenggang ^a,b   Yao, Jun ^a,b   Gong, Likun ^a   Nohmi, Takehiko ^c   Gu, Jun ^d,e   Zhou, Wanhong ^f   Zheng, Saijing ^f   Ren, Jin ^a  

^a SHANGHAI INSTITUTE OF MATERIA MEDICA   (China)

^b UNIVERSITY OF CHINESE ACADEMY OF SCIENCES   (China)

^c NATIONAL INSTITUTE OF HEALTH SCIENCES   (Japan)

^d WADSWORTH CENTER   (United States)

^e STATE UNIVERSITY OF NEW YORK   (United States)

^f Shanghai Tobacco Group Co Ltd   (China)

Author keywords

Gene mutation assay; Gpt delta mouse; Hepatic P450; NNK

Indexed keywords

4 (METHYLNITROSAMINO) 1 (3 PYRIDYL) 1 BUTANONE; CYTOCHROME P450; CYTOCHROME P450 REDUCTASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CARCINOGEN TESTING; CHEMICAL MUTAGENESIS; CONTROLLED STUDY; ENZYME ACTIVATION; ENZYME ACTIVITY; GENE FREQUENCY; GENE MUTATION; GENOTOXICITY; INDUCED MUTATION; LIVER; LUNG; MOUSE; NONHUMAN; PRIORITY JOURNAL; TISSUE DISTRIBUTION; TISSUE LEVEL; TOXICOKINETICS;

ANIMALS; CARCINOGENS; LIVER; LUNG; MICE; MICE, TRANSGENIC; MUTAGENESIS; MUTAGENICITY TESTS; NADPH-FERRIHEMOPROTEIN REDUCTASE; NITROSAMINES; TISSUE DISTRIBUTION;

MUS;

EID: 84871185442     PISSN: 03405761     EISSN: 14320738     Source Type: Journal    
DOI: 10.1007/s00204-012-0891-6     Document Type: Article

References (92)

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2. Arlt VM, Stiborova M, Henderson CJ et al (2008) Metabolic activation of benzo[a]pyrene in vitro by hepatic cytochrome P450 contrasts with detoxification in vivo: experiments with hepatic cytochrome P450 reductase null mice. Carcinogenesis 29(3):656-665. doi:10.1093/carcin/bgn002.
3. Arlt VM, Singh R, Stiborova M et al (2011) Effect of hepatic cytochrome P450 (P450) oxidoreductase deficiency on 2-amino- 1-methyl-6-phenylimidazo[4, 5-b]pyridine-DNA adduct formation in P450 reductase conditional null mice. Drug Metab Dispos 39(12):2169-2173. doi:10.1124/dmd.111.041343.
4. Baird WM, Hooven LA, Mahadevan B (2005) Carcinogenic polycyclic aromatic hydrocarbon-DNA adducts and mechanism of action. Environ Mol Mutagen 45(2-3):106-114. doi:10.1002/em.20095.
5. Boverhof DR, Chamberlain MP, Elcombe CR et al (2011) Transgenic animal models in toxicology: historical perspectives and future outlook. Toxicol Sci 121(2):207-233. doi:10.1093/toxsci/kfr075.
6. Brown PJ, Massey TE (2009) In vivo treatment with 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK) induces organ-specific alterations in in vitro repair of DNA pyridyloxobutylation. Mutat Res 663(1-2):15-21. doi:10.1016/j.mrfmmm.2008.12.008.
7. Cariello NF (1994) Software for the analysis of mutations at the human hprt gene. Mutat Res 312:173-185.
8. Cleaver JE (1969) Xeroderma pigmentosum: a human disease in which an initial stage of DNA repair is defective. Proc Natl Acad Sci U S A 63(2):428-435.
9. Coon MJ (2005) Cytochrome P450: nature's most versatile biological catalyst. Annu Rev Pharmacol Toxicol 45:1-25. doi:10.1146/annurev.pharmtox.45. 120403.100030.
10. Dalton TP, Dieter MZ, Matlib RS et al (2000) Targeted knockout of Cyp1a1 gene does not alter hepatic constitutive expression of other genes in the mouse [Ah] battery. Biochem Biophys Res Commun 267(1):184-189. doi:10.1006/bbrc.1999. 1913.
11. Evans WE, Relling MV (1999) Pharmacogenomics: translating functional genomics into rational therapeutics. Science 286 (5439): 487-491.
12. Grover PL, Sims P (1968) Enzyme-catalysed reactions of polycyclic hydrocarbons with deoxyribonucleic acid and protein in vitro. Biochem J 110(1):159-160.
13. Gu J, Weng Y, Zhang QY et al (2003) Liver-specific deletion of the NADPH-cytochrome P450 reductase gene: impact on plasma cholesterol homeostasis and the function and regulation of microsomal cytochrome P450 and heme oxygenase. J Biol Chem 278(28):25895-25901. doi:10.1074/jbc.M303125200.
14. Gu J, Cui H, Behr M et al (2005) In vivo mechanisms of tissueselective drug toxicity: effects of liver-specific knockout of the NADPH-cytochrome P450 reductase gene on acetaminophen toxicity in kidney, lung, and nasal mucosa. Mol Pharmacol 67(3):623-630. doi:10.1124/mol.104.007898.
15. Gu J, Chen CS, Wei Y et al (2007) A mouse model with liver-specific deletion and global suppression of the NADPH-cytochrome P450 reductase gene: characterization and utility for in vivo studies of cyclophosphamide disposition. J Pharmacol Exp Ther 321(1):9-17. doi:10.1124/jpet.106.118240.
16. Hang B (2010) Formation and repair of tobacco carcinogen-derived bulky DNA adducts. J Nucleic Acids 2010:709521. doi:10.4061/2010/709521.
17. Hecht SS (1998) Biochemistry, biology, and carcinogenicity of tobacco-specific N-nitrosamines. Chem Res Toxicol 11(6):559- 603. doi:10.1021/tx980005y.
18. Hecht SS, Trushin N, Rigotty J et al (1996) Complete inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced rat lung tumorigenesis and favorable modification of biomarkers by phenethyl isothiocyanate. Cancer Epidemiol Biomarkers Prev 5(8):645-652.
19. Heddle JA, Dean S, Nohmi T et al (2000) In vivo transgenic mutation assays. Environ Mol Mutagen 35(3):253-259. doi:10.1002/(SICI)1098-2280(2000)35: 3\253:AID-EM11[3.0.CO;2-J.
20. Henderson CJ, Otto DM, Carrie D et al (2003) Inactivation of the hepatic cytochrome P450 system by conditional deletion of hepatic cytochrome P450 reductase. J Biol Chem 278(15): 13480-13486. doi:10.1074/jbc.M212087200.
21. Horiguchi M, Masumura K, Ikehata H et al (1999) UVB-induced gpt mutations in the skin of gpt delta transgenic mice. Environ Mol Mutagen 34(2-3):72-79. doi:10.1002/(SICI)1098-2280(1999) 34:2/3\72:AID-EM3[3.0.CO;2-8.
22. Ikeda M, Masumura K, Sakamoto Y et al (2007) Combined genotoxic effects of radiation and a tobacco-specific nitrosamine in the lung of gpt delta transgenic mice. Mutat Res 626(1-2):15-25. doi:10.1016/j.mrgentox.2006.07.003.
23. Jalas JR, Hecht SS, Murphy SE (2005) Cytochrome P450 enzymes as catalysts of metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)- 1-butanone, a tobacco specific carcinogen. Chem Res Toxicol 18(2):95-110. doi:10.1021/tx049847p.
24. Kaufmann WK (1989) Pathways of human cell post-replication repair. Carcinogenesis 10(1):1-11.
25. Lao Y, Villalta PW, Sturla SJ, Wang M, Hecht SS (2006) Quantitation of pyridyloxobutyl DNA adducts of tobaccospecific nitrosamines in rat tissue DNA by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Chem Res Toxicol 19(5):674-682. doi:10.1021/tx050351x.
26. Levova K, Moserova M, Kotrbova V et al (2011) Role of cytochromes P450 1A1/2 in detoxication and activation of carcinogenic aristolochic acid I: studies with the hepatic NADPH:cytochrome P450 reductase null (HRN) mouse model. Toxicol Sci 121(1):43-56. doi:10.1093/toxsci/kfr050.
27. Masumura K, Matsui M, Katoh M et al (1999) Spectra of gpt mutations in ethylnitrosourea-treated and untreated transgenic mice. Environ Mol Mutagen 34(1):1-8.
28. Masumura K, Horiguchi M, Nishikawa A et al (2003) Low dose genotoxicity of 2-amino-3, 8-dimethylimidazo[4, 5-f]quinoxaline (MeIQx) in gpt delta transgenic mice. Mutat Res 541(1-2): 91-102.
29. Minnick DT, Gerson SL, Dumenco LL, Veigl ML, Sedwick WD (1993) Specificity of bischloroethylnitrosourea-induced mutation in a Chinese hamster ovary cell line transformed to express human O6-alkylguanine-DNA alkyltransferase. Cancer Res 53 (5):997-1003.
30. Nebert DW, Dalton TP (2006) The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis. Nat Rev Cancer 6(12):947-960. doi:10.1038/nrc2015.
31. Nohmi T (2000) [Development of novel genotoxicity assays by genetic engineering methods]. Kokuritsu Iyakuhin Shokuhin Eisei Kenkyusho Hokoku(118):1-20.
32. Nohmi T, Masumura K (2004) Gpt delta transgenic mouse: a novel approach for molecular dissection of deletion mutations in vivo. Adv Biophys 38:97-121.
33. Nohmi T, Masumura K (2005) Molecular nature of intrachromosomal deletions and base substitutions induced by environmental mutagens. Environ Mol Mutagen 45(2-3):150-161. doi:10.1002/em.20110.
34. Nohmi T, Katoh M, Suzuki H et al (1996) A new transgenic mouse mutagenesis test system using Spi- and 6-thioguanine selections. Environ Mol Mutagen 28(4):465-470. doi:10.1002/(SICI)1098- 2280(1996)28:4\465:AID-EM24[3.0. CO;2-C.
35. Pineau T, Costet P, Puel O et al (1998) Knockout animals in toxicology: assessment of toxin bioactivation pathways using mice deficient in xenobiotic metabolizing enzymes. Toxicol Lett 102-103:459-464.
36. Shane BS, Smith-Dunn DL, deBoer JG, Glickman BW, Cunningham ML (2000) Subchronic administration of phenobarbital alters the mutation spectrum of lacI in the livers of Big Blue transgenic mice. Mutat Res 448(1):69-80.
37. Singh VK, Ganesh L, Cunningham ML, Shane BS (2001) Comparison of the mutant frequencies and mutation spectra of three nongenotoxic carcinogens, oxazepam, phenobarbital, and Wyeth 14, 643, at the lambdacII locus in Big Blue transgenic mice. Biochem Pharmacol 62(6):685-692.
38. Smith TJ, Guo ZY, Thomas PE et al (1990) Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in mouse lung microsomes and its inhibition by isothiocyanates. Cancer Res 50(21):6817-6822.
39. Sturla SJ, Scott J, Lao Y, Hecht SS, Villalta PW (2005) Mass spectrometric analysis of relative levels of pyridyloxobutylation adducts formed in the reaction of DNA with a chemically activated form of the tobacco-specific carcinogen 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone. Chem Res Toxicol 18(6): 1048-1055. doi:10.1021/tx050028u.
40. Su T, Bao Z, Zhang QY, Smith TJ, Hong JY, Ding X (2000) Human cytochrome P450 CYP2A13: predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)- 1-butanone. Cancer Res 60(18):5074-5079.
41. Takeuchi H, Saoo K, Yokohira M et al (2003) Pretreatment with 8-methoxypsoralen, a potent human CYP2A6 inhibitor, strongly inhibits lung tumorigenesis induced by 4-(methylnitrosamino)-1- (3-pyridyl)-1-butanone in female A/J mice. Cancer Res 63(22): 7581-7583.
42. Thybaud V, Dean S, Nohmi T et al (2003) In vivo transgenic mutation assays. Mutat Res 540(2):141-151.
43. Uno S, Dalton TP, Derkenne S et al (2004) Oral exposure to benzo[a]pyrene in the mouse: detoxication by inducible cytochrome P450 is more important than metabolic activation. Mol Pharmacol 65(5):1225-1237. doi:10.1124/mol.65.5.1225.
44. Weng Y, Fang C, Turesky RJ, Behr M, Kaminsky LS, Ding X (2007) Determination of the role of target tissue metabolism in lung carcinogenesis using conditional cytochrome P450 reductasenull mice. Cancer Res 67(16):7825-7832. doi:10.1158/0008- 5472.CAN-07-1006.
45. Wu L, Gu J, Weng Y et al (2003) Conditional knockout of the mouse NADPH-cytochrome p450 reductase gene. Genesis 36(4):177- 181. doi:10.1002/gene.10214.
46. Xiao Y, Ge M, Xue X et al (2008) Hepatic cytochrome P450 s metabolize aristolochic acid and reduce its kidney toxicity. Kidney Int 73(11):1231-1239.
47. Arlt VM, Stiborova M, Henderson CJ et al (2005) Environmental pollutant and potent mutagen 3-nitrobenzanthrone forms DNA adducts after reduction by NAD(P)H:quinone oxidoreductase and conjugation by acetyltransferases and sulfotransferases in human hepatic cytosols. Cancer Res 65(7):2644-2652. doi:10. 1158/0008-5472.CAN-04-3544.
48. Arlt VM, Stiborova M, Henderson CJ et al (2008) Metabolic activation of benzo[a]pyrene in vitro by hepatic cytochrome P450 contrasts with detoxification in vivo: experiments with hepatic cytochrome P450 reductase null mice. Carcinogenesis 29(3):656-665. doi:10.1093/carcin/bgn002.
49. Arlt VM, Singh R, Stiborova M et al (2011) Effect of hepatic cytochrome P450 (P450) oxidoreductase deficiency on 2-amino- 1-methyl-6-phenylimidazo[4, 5-b]pyridine-DNA adduct formation in P450 reductase conditional null mice. Drug Metab Dispos 39(12):2169-2173. doi:10.1124/dmd.111.041343.
50. Baird WM, Hooven LA, Mahadevan B (2005) Carcinogenic polycyclic aromatic hydrocarbon-DNA adducts and mechanism of action. Environ Mol Mutagen 45(2-3):106-114. doi:10.1002/em.20095.
51. Boverhof DR, Chamberlain MP, Elcombe CR et al (2011) Transgenic animal models in toxicology: historical perspectives and future outlook. Toxicol Sci 121(2):207-233. doi:10.1093/toxsci/kfr075.
52. Brown PJ, Massey TE (2009) In vivo treatment with 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK) induces organ-specific alterations in in vitro repair of DNA pyridyloxobutylation. Mutat Res 663(1-2):15-21. doi:10.1016/j.mrfmmm.2008.12.008.
53. Cariello NF (1994) Software for the analysis of mutations at the human hprt gene. Mutat Res 312:173-185.
54. Cleaver JE (1969) Xeroderma pigmentosum: a human disease in which an initial stage of DNA repair is defective. Proc Natl Acad Sci U S A 63(2):428-435.
55. Coon MJ (2005) Cytochrome P450: nature's most versatile biological catalyst. Annu Rev Pharmacol Toxicol 45:1-25. doi:10.1146/annurev.pharmtox.45. 120403.100030.
56. Dalton TP, Dieter MZ, Matlib RS et al (2000) Targeted knockout of Cyp1a1 gene does not alter hepatic constitutive expression of other genes in the mouse [Ah] battery. Biochem Biophys Res Commun 267(1):184-189. doi:10.1006/bbrc.1999. 1913.
57. Evans WE, Relling MV (1999) Pharmacogenomics: translating functional genomics into rational therapeutics. Science 286 (5439): 487-491.
58. Grover PL, Sims P (1968) Enzyme-catalysed reactions of polycyclic hydrocarbons with deoxyribonucleic acid and protein in vitro. Biochem J 110(1):159-160.
59. Gu J, Weng Y, Zhang QY et al (2003) Liver-specific deletion of the NADPH-cytochrome P450 reductase gene: impact on plasma cholesterol homeostasis and the function and regulation of microsomal cytochrome P450 and heme oxygenase. J Biol Chem 278(28):25895-25901. doi:10.1074/jbc.M303125200.
60. Gu J, Cui H, Behr M et al (2005) In vivo mechanisms of tissueselective drug toxicity: effects of liver-specific knockout of the NADPH-cytochrome P450 reductase gene on acetaminophen toxicity in kidney, lung, and nasal mucosa. Mol Pharmacol 67(3):623-630. doi:10.1124/mol.104.007898.
61. Gu J, Chen CS, Wei Y et al (2007) A mouse model with liver-specific deletion and global suppression of the NADPH-cytochrome P450 reductase gene: characterization and utility for in vivo studies of cyclophosphamide disposition. J Pharmacol Exp Ther 321(1):9-17. doi:10.1124/jpet.106.118240.
62. Hang B (2010) Formation and repair of tobacco carcinogen-derived bulky DNA adducts. J Nucleic Acids 2010:709521. doi:10.4061/2010/709521.
63. Hecht SS (1998) Biochemistry, biology, and carcinogenicity of tobacco-specific N-nitrosamines. Chem Res Toxicol 11(6):559- 603. doi:10.1021/tx980005y.
64. Hecht SS, Trushin N, Rigotty J et al (1996) Complete inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced rat lung tumorigenesis and favorable modification of biomarkers by phenethyl isothiocyanate. Cancer Epidemiol Biomarkers Prev 5(8):645-652.
65. Heddle JA, Dean S, Nohmi T et al (2000) In vivo transgenic mutation assays. Environ Mol Mutagen 35(3):253-259. doi:10.1002/(SICI)1098-2280(2000)35: 3\253:AID-EM11[3.0.CO;2-J.
66. Henderson CJ, Otto DM, Carrie D et al (2003) Inactivation of the hepatic cytochrome P450 system by conditional deletion of hepatic cytochrome P450 reductase. J Biol Chem 278(15): 13480-13486. doi:10.1074/jbc.M212087200.
67. Horiguchi M, Masumura K, Ikehata H et al (1999) UVB-induced gpt mutations in the skin of gpt delta transgenic mice. Environ Mol Mutagen 34(2-3):72-79. doi:10.1002/(SICI)1098-2280(1999) 34:2/3\72:AID-EM3[3.0.CO;2-8.
68. Ikeda M, Masumura K, Sakamoto Y et al (2007) Combined genotoxic effects of radiation and a tobacco-specific nitrosamine in the lung of gpt delta transgenic mice. Mutat Res 626(1-2):15-25. doi:10.1016/j.mrgentox.2006.07.003.
69. Jalas JR, Hecht SS, Murphy SE (2005) Cytochrome P450 enzymes as catalysts of metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)- 1-butanone, a tobacco specific carcinogen. Chem Res Toxicol 18(2):95-110. doi:10.1021/tx049847p.
70. Kaufmann WK (1989) Pathways of human cell post-replication repair. Carcinogenesis 10(1):1-11.
71. Lao Y, Villalta PW, Sturla SJ, Wang M, Hecht SS (2006) Quantitation of pyridyloxobutyl DNA adducts of tobaccospecific nitrosamines in rat tissue DNA by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Chem Res Toxicol 19(5):674-682. doi:10.1021/tx050351x.
72. Levova K, Moserova M, Kotrbova V et al (2011) Role of cytochromes P450 1A1/2 in detoxication and activation of carcinogenic aristolochic acid I: studies with the hepatic NADPH:cytochrome P450 reductase null (HRN) mouse model. Toxicol Sci 121(1):43-56. doi:10.1093/toxsci/kfr050.
73. Masumura K, Matsui M, Katoh M et al (1999) Spectra of gpt mutations in ethylnitrosourea-treated and untreated transgenic mice. Environ Mol Mutagen 34(1):1-8.
74. Masumura K, Horiguchi M, Nishikawa A et al (2003) Low dose genotoxicity of 2-amino-3, 8-dimethylimidazo[4, 5-f]quinoxaline (MeIQx) in gpt delta transgenic mice. Mutat Res 541(1-2): 91-102.
75. Minnick DT, Gerson SL, Dumenco LL, Veigl ML, Sedwick WD (1993) Specificity of bischloroethylnitrosourea-induced mutation in a Chinese hamster ovary cell line transformed to express human O6-alkylguanine-DNA alkyltransferase. Cancer Res 53 (5):997-1003.
76. Nebert DW, Dalton TP (2006) The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis. Nat Rev Cancer 6(12):947-960. doi:10.1038/nrc2015.
77. Nohmi T (2000) [Development of novel genotoxicity assays by genetic engineering methods]. Kokuritsu Iyakuhin Shokuhin Eisei Kenkyusho Hokoku(118):1-20.
78. Nohmi T, Masumura K (2004) Gpt delta transgenic mouse: a novel approach for molecular dissection of deletion mutations in vivo. Adv Biophys 38:97-121.
79. Nohmi T, Masumura K (2005) Molecular nature of intrachromosomal deletions and base substitutions induced by environmental mutagens. Environ Mol Mutagen 45(2-3):150-161. doi:10.1002/em.20110.
80. Nohmi T, Katoh M, Suzuki H et al (1996) A new transgenic mouse mutagenesis test system using Spi- and 6-thioguanine selections. Environ Mol Mutagen 28(4):465-470. doi:10.1002/(SICI)1098- 2280(1996)28:4\465:AID-EM24[3.0. CO;2-C.
81. Pineau T, Costet P, Puel O et al (1998) Knockout animals in toxicology: assessment of toxin bioactivation pathways using mice deficient in xenobiotic metabolizing enzymes. Toxicol Lett 102-103:459-464.
82. Shane BS, Smith-Dunn DL, deBoer JG, Glickman BW, Cunningham ML (2000) Subchronic administration of phenobarbital alters the mutation spectrum of lacI in the livers of Big Blue transgenic mice. Mutat Res 448(1):69-80.
83. Singh VK, Ganesh L, Cunningham ML, Shane BS (2001) Comparison of the mutant frequencies and mutation spectra of three nongenotoxic carcinogens, oxazepam, phenobarbital, and Wyeth 14, 643, at the lambdacII locus in Big Blue transgenic mice. Biochem Pharmacol 62(6):685-692.
84. Smith TJ, Guo ZY, Thomas PE et al (1990) Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in mouse lung microsomes and its inhibition by isothiocyanates. Cancer Res 50(21):6817-6822.
85. Sturla SJ, Scott J, Lao Y, Hecht SS, Villalta PW (2005) Mass spectrometric analysis of relative levels of pyridyloxobutylation adducts formed in the reaction of DNA with a chemically activated form of the tobacco-specific carcinogen 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone. Chem Res Toxicol 18(6): 1048-1055. doi:10.1021/tx050028u.
86. Su T, Bao Z, Zhang QY, Smith TJ, Hong JY, Ding X (2000) Human cytochrome P450 CYP2A13: predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)- 1-butanone. Cancer Res 60(18):5074-5079.
87. Takeuchi H, Saoo K, Yokohira M et al (2003) Pretreatment with 8-methoxypsoralen, a potent human CYP2A6 inhibitor, strongly inhibits lung tumorigenesis induced by 4-(methylnitrosamino)-1- (3-pyridyl)-1-butanone in female A/J mice. Cancer Res 63(22): 7581-7583.
88. Thybaud V, Dean S, Nohmi T et al (2003) In vivo transgenic mutation assays. Mutat Res 540(2):141-151.
89. Uno S, Dalton TP, Derkenne S et al (2004) Oral exposure to benzo[a]pyrene in the mouse: detoxication by inducible cytochrome P450 is more important than metabolic activation. Mol Pharmacol 65(5):1225-1237. doi:10.1124/mol.65.5.1225.
90. Weng Y, Fang C, Turesky RJ, Behr M, Kaminsky LS, Ding X (2007) Determination of the role of target tissue metabolism in lung carcinogenesis using conditional cytochrome P450 reductasenull mice. Cancer Res 67(16):7825-7832. doi:10.1158/0008- 5472.CAN-07-1006.
91. Wu L, Gu J, Weng Y et al (2003) Conditional knockout of the mouse NADPH-cytochrome p450 reductase gene. Genesis 36(4):177- 181. doi:10.1002/gene.10214.
92. Xiao Y, Ge M, Xue X et al (2008) Hepatic cytochrome P450 s metabolize aristolochic acid and reduce its kidney toxicity. Kidney Int 73(11):1231-1239.