Mouse cytochrome P450 (Cyp3a11): predominant expression in liver and capacity to activate aflatoxin B1.
S1 mapping analysis for the expression of Cyp3a11 and Cyp3a13 indicated that Cyp3a11 mRNA is predominantly expressed in mouse liver, compared with that of Cyp3a13. In addition, all of six inducers, such as dexamethasone, 3-methylcholanthrene, phenobarbital, polychlorinated biphenyl, pregnenolone 16 alpha-carbonitrile, and rifampicin, increased the expression of the Cyp3a11 mRNA more extensively than that of Cyp3a13. The level of mRNAs corresponding to Cyp3a11 and Cyp3a13 reached the maximum level between 4 and 8 weeks after birth. Cyp3a11 enzyme was expressed into CR119 cells which had been established as a cell line stably expressing NADPH-cytochrome P450 reductase cDNA of guinea pigs. These transformants showed aflatoxin B1-dependent cytotoxicity in proportion to the amounts of Cyp3a11 mRNA. This cytotoxicity was enhanced by 7,8-benzoflavone, a known activator of CYP3A protein. Based on these results, we confirm that CYP3A in the mouse, which is an animal species known to be relatively insensitive to aflatoxin B1 genotoxicity, can activate this mycotoxin efficiently.
Yanagimoto
T
T
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
Itoh
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S
Sawada
M
M
Kamataki
T
T
D016604:Aflatoxin B1 / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015870:Gene Expression; D008658:Inactivation, Metabolic; D008099:Liver / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics
D008565:Membrane Proteins; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D001189:Aryl Hydrocarbon Hydroxylases; C496508:Cyp3a11 protein, mouse; C496509:Cyp3a13 protein, mouse; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating