Takeishi K, Okuno-Kaneda S, Seno T
Mutat Res. 1979 Oct;62(3):425-37. doi: 10.1016/0027-5107(79)90038-1.
2-Acetylaminofluorene (AAF) was highly mutagenic to Salmonella typhimurium strain TA98, when activated by a liver post-mitochondrial supernatant fraction (S9 fraction) from guinea-pigs, in spite of the resistance of this species to AAF carcinogenesis and the low capacity of the liver of this species for N-hydroxylation of AAF. The mutagenicity was comparable to or higher than that resulting from activation by mouse- or rat-liver S9 fraction, and was not enchanced by treatment with cytochrome P-450 inducers, a combination of phenobarbital and 5,6-benzoflavone. In an attempt to understand this unexpected result we examined whether a cytochrome P-450 mixed-function oxidase system participated in the mutagenic activation of AAF by guinea-pig liver, as it does in the case of mouse liver. The mutagenic activation was: (1) completely dependent on the addition of a co-factor, NADPH, to the mutation assay system, (2) completely suppressed by antiserum against NADPH--cytochrome c reductase, and (3) sensitive to a cytochrome P-450 inhibitor, 7,8-benzoflavone. These results indicate that the cytochrome P-450 enzyme system is essentially involved even in the mutagenic activation of AAF by guinea-pig-liver S9 fraction. Based on both the present and other data, the mechanism of the mutagenic activation is discussed to explain the observed high mutagenic potential of AAF in the presence of guinea-pig-liver S9 fraction.
2-乙酰氨基芴（AAF）对鼠伤寒沙门氏菌TA98菌株具有高度致突变性，当由豚鼠肝脏线粒体后上清液组分（S9组分）激活时，尽管该物种对AAF致癌作用具有抗性且其肝脏对AAF的N-羟基化能力较低。其致突变性与由小鼠或大鼠肝脏S9组分激活所产生的致突变性相当或更高，并且用细胞色素P-450诱导剂、苯巴比妥和5,6-苯并黄酮的组合处理后并未增强。为了理解这一意外结果，我们研究了细胞色素P-450混合功能氧化酶系统是否像在小鼠肝脏中那样参与豚鼠肝脏对AAF的致突变激活。致突变激活表现为：（1）完全依赖于向突变检测系统中添加辅因子NADPH，（2）被抗NADPH-细胞色素c还原酶抗血清完全抑制，以及（3）对细胞色素P-450抑制剂7,8-苯并黄酮敏感。这些结果表明，细胞色素P-450酶系统甚至在豚鼠肝脏S9组分对AAF的致突变激活中也起着重要作用。基于目前的数据和其他数据，讨论了致突变激活的机制，以解释在豚鼠肝脏S9组分存在下观察到的AAF的高致突变潜力。
