Davis C D, Adamson R H, Snyderwine E G
Laboratory of Experimental Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-0037.
Cancer Lett. 1993 Sep 30;73(2-3):95-104. doi: 10.1016/0304-3835(93)90250-d.
A number of mutagens and carcinogens have been isolated from cooked meats. In the current study we investigated the ability of hepatic microsomes from cynomolgus monkeys, Fischer-344 rats and humans to metabolically activate these compounds. Monkeys had almost no capacity to activate the quinoxaline-type compounds to mutagens in the Ames test relative to rats and humans but were able to activate the quinoline, pyridoindole and pyridoimidazole compounds. Differences in the mutagenicity of the quinoline and quinoxaline compounds by monkeys and rats was related to differences in cytochrome P-450-mediated N-oxidation between the species. This suggests that monkeys and rats may have different hepatic cytochrome P-450 isozymes, which are important for the metabolic activation of quinolines and quinoxalines, or that the orthologous monkey cytochromes show a select substrate specificity for the quinolines over the quinoxalines.
已从熟肉中分离出多种诱变剂和致癌物。在本研究中,我们研究了食蟹猴、Fischer-344大鼠和人类的肝微粒体代谢激活这些化合物的能力。相对于大鼠和人类,在艾姆斯试验中,猴子几乎没有将喹喔啉类化合物激活为诱变剂的能力,但能够激活喹啉、吡啶并吲哚和吡啶并咪唑类化合物。猴子和大鼠对喹啉和喹喔啉化合物致突变性的差异与物种间细胞色素P-450介导的N-氧化差异有关。这表明猴子和大鼠可能具有不同的肝细胞色素P-450同工酶,这些同工酶对喹啉和喹喔啉的代谢激活很重要,或者猴子的直系同源细胞色素对喹啉显示出比对喹喔啉更具选择性的底物特异性。