Mori Y, Yamazaki H, Toyoshi K, Maruyama H, Konishi Y
Mutat Res. 1986 May;160(3):159-69. doi: 10.1016/0027-5107(86)90125-9.
The mutagenic potential of 7 carcinogenic N-nitrosopropylamines was examined by the Ames liquid incubation assay, using lung and pancreas 9000 X g supernatant (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) and N-nitrosomethyl(2-oxopropyl)amine (MOP) showed positive mutagenicity in strain TA100 in the presence of lung S9 from each of the uninduced animals and humans. Besides the 3 N-nitrosopropylamines, N-nitrosomethyl(2-hydroxypropyl)amine (MHP) was also positive in the presence of lung S9 from polychlorinated biphenyl (PCB)-induced rats, hamsters and mice. On the other hand, in the presence of pancreas S9 from uninduced or PCB-induced animals, only HPOP and BOP showed positive mutagenicity. In contrast, N-nitrosobis(2-hydroxypropyl)amine (BHP), N-nitrosobis(2-acetoxypropyl)amine (BAP) and N-nitroso-2,6-dimethylmorpholine (NDMM) showed negative mutagenicity in the presence of lung and pancreas S9 from either uninduced or PCB-induced animals and humans. HPOP was a direct-acting mutagen, and lung and pancreas S9 from 5 animal species and man did not affect the activity. BOP was mutagenic even in the presence of bovine serum albumin. The mutagenic activation of MHP by lung S9 from PCB-induced rats, hamsters and mice was completely inhibited by preincubation in an atmosphere of carbon monoxide or by addition of cytochrome c or metyrapone to the S9 mixture, whereas 7,8-benzoflavone totally lacked this effect. However, that of MOP was insensitive to these inhibitors. These results of mutagenicity assay indicate that only the methyl derivatives of N-nitrosopropylamines, MHP and MOP are activated by the lung from 5 animal species and man, whereas the pancreas from all the tested animals did not activate the 7 N-nitrosopropylamines to mutagens, and that the phenobarbital-inducible major cytochrome P-450 in the lung of rodents is involved in the mutagenic activation of MHP.
通过Ames液体培养试验检测了7种致癌性N-亚硝基丙胺的致突变潜力，使用大鼠、仓鼠、小鼠、兔子、猴子和人类的肺和胰腺9000×g上清液（S9）组分进行代谢活化。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）和N-亚硝基甲基（2-氧代丙基）胺（MOP）在未诱导的动物和人类的肺S9存在下，在TA100菌株中显示出阳性致突变性。除了这3种N-亚硝基丙胺外，N-亚硝基甲基（2-羟丙基）胺（MHP）在多氯联苯（PCB）诱导的大鼠、仓鼠和小鼠的肺S9存在下也呈阳性。另一方面，在未诱导或PCB诱导的动物的胰腺S9存在下，只有HPOP和BOP显示出阳性致突变性。相比之下，N-亚硝基双（2-羟丙基）胺（BHP）、N-亚硝基双（2-乙酰氧基丙基）胺（BAP）和N-亚硝基-2,6-二甲基吗啉（NDMM）在未诱导或PCB诱导的动物和人类的肺和胰腺S9存在下显示出阴性致突变性。HPOP是一种直接作用的诱变剂，5种动物物种和人类的肺和胰腺S9不影响其活性。BOP即使在存在牛血清白蛋白的情况下也具有致突变性。PCB诱导的大鼠、仓鼠和小鼠的肺S9对MHP的诱变活化作用，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或甲吡酮可完全抑制，而7,8-苯并黄酮则完全没有这种作用。然而，MOP的诱变活化对这些抑制剂不敏感。这些致突变性试验结果表明，只有N-亚硝基丙胺的甲基衍生物MHP和MOP能被5种动物物种和人类的肺激活，而所有受试动物的胰腺都不能将这7种N-亚硝基丙胺激活为诱变剂，并且啮齿动物肺中苯巴比妥诱导的主要细胞色素P-450参与了MHP的诱变活化。
