Molecular cloning and functional expression of a mouse cytochrome P-450 (Cyp3a-13): examination of Cyp3a-13 enzyme to activate aflatoxin B1 (AFB1).
A cDNA encoding a novel member of the cytochrome P-450 superfamily, Cyp3a-13, has been isolated from mouse liver cDNA library by hybridization screening. The Cyp3a-13 encoded 503 amino acid residues and shared 71% amino acid identity with Cyp3a-11. When Cyp3a-13 cDNA was expressed in CR119 cells which had been established as a cell line stably expressing NADPH-cytochrome P-450 reductase cDNA of guinea pigs, aflatoxin B1-dependent cytotoxicity was observed. This cytotoxicity was enhanced by alpha-naphthoflavone (7,8-benzoflavone), which is known to augment the CYP3A enzymatic activity. The results indicate that CYP3A in mice, which are relatively insensitive to aflatoxin B1, can activate aflatoxin B1 to a genotoxic product.
Yanagimoto
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T
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
Itoh
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S
Sawada
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M
Hashimoto
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H
Kamataki
T
T
D016604:Aflatoxin B1 / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D002460:Cell Line / Q000201:enzymology; D003001:Cloning, Molecular; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D018076:DNA, Complementary / Q000737:chemistry; D006168:Guinea Pigs; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism
D001571:Benzoflavones; D018076:DNA, Complementary; D008565:Membrane Proteins; C011512:alpha-naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; C496509:Cyp3a13 protein, mouse; D051544:Cytochrome P-450 CYP3A; D009251:NADPH-Ferrihemoprotein Reductase