Schmezer P, Pool B L, Preussmann R, Schmähl D
Institute for Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.
IARC Sci Publ. 1987(84):270-3.
DNA single-strand breaks (SSB) were induced in metabolically competent primary hepatocytes from rats, hamsters and pigs by a series of N-nitrosamines with organ-specific activities. Both hepatotrophic and nonhepatotropic carcinogens were genotoxic in the liver cells of all three species. Nonhepatotropic compounds were active at relatively lower doses than liver carcinogens in all species tested, substantiating many previous findings that organ-specific activation is not the primary determining factor of organ susceptibility to cancer. In 11 experiments of almost identical quality, the degree of SSB induced by 6.25 mumol N-nitrosodimethylamine varied by 75%. This high interindividual variability, even among hepatocytes derived from a single rat strain, indicates that the slight differences seen between rat, hamster and pig hepatocytes are not necessarily due to differences in species susceptibility.
一系列具有器官特异性活性的N-亚硝胺在大鼠、仓鼠和猪的代谢活性原代肝细胞中诱导产生DNA单链断裂(SSB)。肝营养性致癌物和非肝营养性致癌物在所有这三个物种的肝细胞中均具有基因毒性。在所有测试物种中,非肝营养性化合物在相对较低剂量时就具有活性,这比肝脏致癌物的活性剂量低,证实了许多先前的研究结果,即器官特异性活化不是器官对癌症易感性的主要决定因素。在11个质量几乎相同的实验中,6.25μmol N-亚硝基二甲胺诱导的SSB程度相差75%。这种高度的个体间变异性,即使在来自单一大鼠品系的肝细胞之间也是如此,表明在大鼠、仓鼠和猪肝细胞之间观察到的细微差异不一定是由于物种易感性的差异。