Yanagimoto T, Itoh S, Sawada M, Hashimoto H, Kamataki T
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
Biochim Biophys Acta. 1994 Dec 15;1201(3):405-10. doi: 10.1016/0304-4165(94)90069-8.
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.
通过杂交筛选从小鼠肝脏cDNA文库中分离出一种编码细胞色素P - 450超家族新成员Cyp3a - 13的cDNA。Cyp3a - 13编码503个氨基酸残基，与Cyp3a - 11的氨基酸同一性为71%。当Cyp3a - 13 cDNA在已建立为稳定表达豚鼠NADPH - 细胞色素P - 450还原酶cDNA的细胞系CR119细胞中表达时，观察到黄曲霉毒素B1依赖性细胞毒性。这种细胞毒性被α - 萘黄酮（7,8 - 苯并黄酮）增强，已知α - 萘黄酮可增强CYP3A酶活性。结果表明，对黄曲霉毒素B1相对不敏感的小鼠中的CYP3A可将黄曲霉毒素B1激活为遗传毒性产物。
