The resistance of putative premalignant liver cell populations, hyperplastic nodules, to the acute cytotoxic effects of some hepatocarcinogens.
The resistance of putative premalignant liver cell populations, hyperplastic nodules, to the acute cytotoxic effects of some hepatocarcinogens.
复制标题
假定的癌前肝细胞群、增生结节对某些肝癌物质的急性细胞毒性作用的抵抗力。
作者：
E. Farber;S. Parker;M. Gruenstein
假设肝癌变可能有一个重要方面的早期选择的致癌物耐药细胞进行了测试，在动物中，假定癌前肝细胞群，增生结节，诱导2-乙酰氨基芴或乙醇。观察到增生性结节对2种肝毒素（CCl 4和二甲基亚硝胺）的急性坏死作用具有抗性，条件是结节周围的肝脏发生肝细胞坏死。此外，虽然[甲基-3H]二甲基亚硝胺在结节和正常肝脏中的摄取程度相同，但在增生结节中与DNA、RNA和蛋白质的相互作用比对照肝脏低约50%。增生结节显示[9- 14 C]-2-乙酰氨基芴的摄取显著减少，这一发现可以解释结节中观察到的[9- 14 C]-2-乙酰氨基芴标记DNA、RNA和蛋白质的大量减少。结果是一致的，并支持这一假设，即新的肝细胞群体出现之前，癌症，在肝癌发生过程中，作为一个重要的生物学特性的抗肝癌的细胞毒性作用。这种耐药性的基础可能是摄入量减少和/或致癌物活化水平降低。
The hypothesis that liver carcinogenesis may have as an important facet the early selection of carcinogen-resistant cells was tested in animals in which putative premalignant hepatocyte populations, hyperplastic nodules, were induced by 2-acetylaminofluorene or by ethionine. Hyperplastic nodules were observed to be resistant to the acute necrogenic effects of 2 hepatotoxins, CCl4 and dimethylnitrosamine, under conditions in which liver cell necrosis occurred in the liver surrounding the nodules. In addition, although [methyl-3H]dimethylnitrosamine was taken up to an equal degree in nodules and normal liver, the interactions with DNA, RNA, and protein in hyperplastic nodules were found to be about 50% less than in control liver. Hyperplastic nodules showed a marked decrease in uptake of [9-14C]-2-acetylaminofluorene, a finding that could account for the large decrease in labeling of DNA, RNA, and protein by [9-14C]-2acetylaminofluorene observed in the nodules. The results are consistent with and support the hypothesis that new hepatocyte populations that appear prior to cancer, during liver carcinogenesis, have as an important biological property a resistance to the cytotoxic effect of hepatocarcinogens. The basis for this resistance might be a decrease in uptake and/or a reduction in the level of activation of carcinogens.