Respective roles of CYP2A5 and CYP2F2 in the bioactivation of 3-methylindole in mouse olfactory mucosa and lung: Studies using Cyp2a5-null and Cyp2f2-null mouse models

Drug Metabolism and Disposition

Volumn 40, Issue 4, 2012, Pages 642-647

  Zhou, Xin ^a,b   D'Agostino, Jaime ^a,b   Li, Lei ^a,b   Moore, Chad D ^c   Yost, Garold S ^c   Ding, Xinxin ^a,b  

^a WADSWORTH CENTER   (United States)

^b STATE UNIVERSITY OF NEW YORK   (United States)

^c UNIVERSITY OF UTAH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

3 GLUTATHIONYLMETHYLINDOLE; 3 HYDROXY 3 METHYLENEINDOLENINE; 3 INDOLEMETHANOL; 3 METHYL 2 GLUTATHIONYLINDOLE; 3 METHYLOXINDOLE; CYTOCHROME P450; CYTOCHROME P450 2A5; CYTOCHROME P450 2F2; GLUTATHIONE; INDOLE DERIVATIVE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; SKATOLE; UNCLASSIFIED DRUG;

ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; CYP2A5 GENE; CYP2F2 GENE; DEHYDROGENATION; DRUG ACTIVATION; ENZYME KINETICS; EPOXIDATION; GENE; IN VITRO STUDY; LUNG; MALE; METABOLISM; METABOLITE; MICROSOME; MOUSE; NONHUMAN; OLFACTORY EPITHELIUM; PRIORITY JOURNAL; PROTEIN FUNCTION; TOXICOKINETICS; WILD TYPE;

ANIMALS; ARYL HYDROCARBON HYDROXYLASES; BIOTRANSFORMATION; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CYTOCHROME P-450 ENZYME SYSTEM; LUNG; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICROSOMES; OLFACTORY MUCOSA; SKATOLE; TANDEM MASS SPECTROMETRY;

MUS;

EID: 84863379737     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.111.044081     Document Type: Article

References (29)

1. Baldwin RM, Jewell WT, Fanucchi MV, Plopper CG, and Buckpitt AR (2004) Comparison of pulmonary/nasal CYP2F expression levels in rodents and rhesus macaque. J Pharmacol Exp Ther 309:127-136. (Pubitemid 38393123)
2. D'Agostino J, Zhuo X, Shadid M, Morgan DG, Zhang X, Humphreys WG, Shu YZ, Yost GS, and Ding X (2009) The pneumotoxin 3-methylindole is a substrate and a mechanism-based inactivator of CYP2A13, a human cytochrome P450 enzyme preferentially expressed in the respiratory tract. Drug Metab Dispos 37:2018-2027.
3. Gu J, Zhang QY, Genter MB, Lipinskas TW, Negishi M, Nebert DW, and Ding X (1998) Purification and characterization of heterologously expressed mouse CYP2A5 and CYP2G1: role in metabolic activation of acetaminophen and 2,6-dichlorobenzonitrile in mouse olfactory mucosal microsomes. J Pharmacol Exp Ther 285:1287-1295. (Pubitemid 28277931)
4. Lanza DL, Code E, Crespi CL, Gonzalez FJ, and Yost GS (1999) Specific dehydrogenation of 3-methylindole and epoxidation of naphthalene by recombinant human CYP2F1 expressed in lymphoblastoid cells. Drug Metab Dispos 27:798-803. (Pubitemid 29297777)
5. Lanza DL and Yost GS (2001) Selective dehydrogenation/oxygenation of 3-methylindole by cytochrome p450 enzymes. Drug Metab Dispos 29:950-953. (Pubitemid 32605908)
6. Li L, Wei Y, Van Winkle L, Zhang QY, Zhou X, Hu J, Xie F, Kluetzman K, and Ding X (2011) Generation and characterization of a Cyp2f2-null mouse and studies on the role of CYP2F2 in naphthalene-induced toxicity in the lung and nasal olfactory mucosa. J Pharmacol Exp Ther 339:62-71.
7. Miller MA and O'Bryan MA (2003) Ultrastructural changes and olfactory deficits during 3-methylindole-induced olfactory mucosal necrosis and repair in mice. Ultrastruct Pathol 27:13-21. (Pubitemid 36293151)
8. Nichols WK, Mehta R, Skordos K, Macé K, Pfeifer AM, Carr BA, Minko T, Burchiel SW, and Yost GS (2003) 3-methylindole-induced toxicity to human bronchial epithelial cell lines. Toxicol Sci 71:229-236. (Pubitemid 36285015)
9. Regal KA, Laws GM, Yuan C, Yost GS, and Skiles GL (2001) Detection and characterization of DNA adducts of 3-methylindole. Chem Res Toxicol 14:1014-1024. (Pubitemid 32800157)
10. Ruangyuttikarn W, Appleton ML, and Yost GS (1991) Metabolism of 3-methylindole in human tissues. Drug Metab Dispos 19:977-984.
11. Shu YZ, Johnson BM, and Yang TJ (2008) Role of biotransformation studies in minimizing metabolism-related liabilities in drug discovery. AAPS J 10:178-192.
12. Skiles GL and Yost GS (1996) Mechanistic studies on the cytochrome P450-catalyzed dehydrogenation of 3-methylindole. Chem Res Toxicol 9:291-297.
13. Su T, Bao Z, Zhang QY, Smith TJ, Hong JY, and 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 60:5074-5079.
14. Su T and Ding X (2004) Regulation of the cytochrome P450 2A genes. Toxicol Appl Pharmacol 199:285-294. (Pubitemid 39208728)
15. Thornton-Manning J, Appleton ML, Gonzalez FJ, and Yost GS (1996) Metabolism of 3-methylindole by vaccinia-expressed P450 enzymes: correlation of 3-methyleneindolenine formation and protein-binding. J Pharmacol Exp Ther 276:21-29. (Pubitemid 26150948)
16. Thornton-Manning JR, Ruangyuttikarn W, Gonzalez FJ, and Yost GS (1991) Metabolic activation of the pneumotoxin, 3-methylindole, by vaccinia-expressed cytochrome P450s. Biochem Biophys Res Commun 181:100-107.
17. Turk MA, Flory W, and Henk WG (1984) Dose response in 3-methylindole-induced bronchiolar epithelial necrosis in mice. Res Commun Chem Pathol Pharmacol 46:351-362.
18. Turk MA, Flory W, and Henk WG (1986) Chemical modulation of 3-methylindole toxicosis in mice: effect on bronchiolar and olfactory mucosal injury. Vet Pathol 23:563-570.
19. Turk MA, Henk WG, and Flory W (1987) 3-Methylindole-induced nasal mucosal damage in mice. Vet Pathol 24:400-403.
20. Weems JM, Cutler NS, Moore C, Nichols WK, Martin D, Makin E, Lamb JG, and Yost GS (2009) 3-Methylindole is mutagenic and a possible pulmonary carcinogen. Toxicol Sci 112:59-67.
21. Weems JM, Lamb JG, D'Agostino J, Ding X, and Yost GS (2010) Potent mutagenicity of 3-methylindole requires pulmonary cytochrome P450-mediated bioactivation: a comparison to the prototype cigarette smoke mutagens B(a)P and NNK. Chem Res Toxicol 23:1682-1690.
22. Xie F, Zhou X, Behr M, Fang C, Horii Y, Gu J, Kannan K, and Ding X (2010) Mechanisms of olfactory toxicity of the herbicide 2,6-dichlorobenzonitrile: essential roles of CYP2A5 and target-tissue metabolic activation. Toxicol Appl Pharmacol 249:101-106.
23. Yao M, Ma L, Humphreys WG, and Zhu M (2008) Rapid screening and characterization of drug metabolites using a multiple ion monitoring-dependent MS/MS acquisition method on a hybrid triple quadrupole-linear ion trap mass spectrometer. J Mass Spectrom 43:1364-1375.
24. Yost GS (1989) Mechanisms of 3-methylindole pneumotoxicity. Chem Res Toxicol 2:273-279.
25. Yost GS (2001) Bioactivation of toxicants by cytochrome p450-mediated dehydrogenation mechanisms. Adv Exp Med Biol 500:53-62.
26. Zhang QY and Ding X (2008) The CYP2F, CYP2G and CYP2J subfamilies, in Cytochromes P450: Role in the Metabolism and Toxicity of Drugs and Other Xenobiotics (Ioannides C, ed) pp 309-353, RSC Publishing, Cambridge, UK.
27. Zhou X, Zhang X, Weng Y, Fang C, Kaminsky L, and Ding X (2009) High abundance of testosterone and salivary androgen-binding protein in the lateral nasal gland of male mice. J Steroid Biochem Mol Biol 117:81-86.
28. Zhou X, Zhuo X, Xie F, Kluetzman K, Shu YZ, Humphreys WG, and Ding X (2010) Role of CYP2A5 in the clearance of nicotine and cotinine: insights from studies on a Cyp2a5-null mouse model. J Pharmacol Exp Ther 332:578-587.
29. Zhou X, Wei Y, Xie F, Laukaitis CM, Karn RC, Kluetzman K, Gu J, Zhang QY, Roberts DW, and Ding X (2011) A novel defensive mechanism against acetaminophen toxicity in the mouse lateral nasal gland: role of CYP2A5-mediated regulation of testosterone homeostasis and salivary androgen-binding protein expression. Mol Pharmacol 79:710-723.