Yamazaki H, Mori Y, Toyoshi K, Nagai H, Koda A, Konishi Y
Jpn J Cancer Res. 1986 Feb;77(2):107-17.
The mutagenic potential of seven carcinogenic N-nitrosopropylamines was examined by means of Ames' preincubation assay using liver 9000 g superanatant (S9) fractions from rats, hamsters, mice, rabbits, monkeys and humans for metabolic activation. N-Nitroso(2-hydroxypropyl) (2-oxopropyl)amine (HPOP), N-nitrosobis(2-oxopropyl)amine (BOP), N-nitrosobis(2-acetoxypropyl)amine (BAP), N-nitroso-2,6-dimethylmorpholine, N-nitrosomethyl(2-hydroxypropyl)amine (MHP) and N-nitrosomethyl(2-oxopropyl)amine all showed positive mutagenicity in strain TA100 in the presence of liver S9 from each of the uninduced animals, but N-nitrosobis(2-hydroxypropyl)amine was negative. The mutagenic activity of MHP was highest with liver S9 from the hamster, but that of BAP was lowest with hamster liver S9. With regard to the activities of the other N-nitrosopropylamines, there were no significant differences among five animal species. In the presence of liver S9 from humans, HPOP, BOP and MHP showed positive mutagenicity. With the exception of HPOP and BOP, the animal or human liver S9-mediated mutagenicity of these N-nitrosopropylamines was almost completely lost upon removal of NADP+ from the assay system, preincubation in an atmosphere of carbon monoxide, or addition of cytochrome c to the S9 mixture. metyrapone decreased the activities of five compounds (except for BOP) by between 29 and 71%, whereas 7,8-benzoflavone was totally lacking in this effect. These results demonstrated that the phenobarbital-inducible major cytochrome P-450 in animal and human livers is involved in the mutagenic activation of the N-nitrosopropylamines.
采用艾姆斯预孵育试验，利用大鼠、仓鼠、小鼠、兔子、猴子和人类肝脏9000g上清液（S9）组分进行代谢活化，检测了七种致癌性N-亚硝基丙胺的诱变潜力。N-亚硝基（2-羟丙基）（2-氧代丙基）胺（HPOP）、N-亚硝基双（2-氧代丙基）胺（BOP）、N-亚硝基双（2-乙酰氧基丙基）胺（BAP）、N-亚硝基-2,6-二甲基吗啉、N-亚硝基甲基（2-羟丙基）胺（MHP）和N-亚硝基甲基（2-氧代丙基）胺在未诱导动物的肝脏S9存在下，在TA100菌株中均显示出阳性诱变性，但N-亚硝基双（2-羟丙基）胺呈阴性。MHP的诱变活性在仓鼠肝脏S9中最高，而BAP在仓鼠肝脏S9中的诱变活性最低。关于其他N-亚硝基丙胺的活性，五种动物物种之间没有显著差异。在人肝脏S9存在下，HPOP、BOP和MHP显示出阳性诱变性。除HPOP和BOP外，如果从检测系统中去除NADP+、在一氧化碳气氛中预孵育或向S9混合物中添加细胞色素c，这些N-亚硝基丙胺的动物或人肝脏S9介导的诱变性几乎完全丧失。美替拉酮使五种化合物（BOP除外）的活性降低了29%至71%，而7,8-苯并黄酮则完全没有这种作用。这些结果表明，动物和人肝脏中苯巴比妥诱导的主要细胞色素P-450参与了N-亚硝基丙胺的诱变活化。
