Verschure P C, Simons J W
Somatic Cell Genet. 1982 May;8(3):307-17. doi: 10.1007/BF01538889.
When mammalian cells are cultured at low concentrations of toxic drugs, they often become phenotypically resistant. We studied whether this phenotypic resistance is due to selection of preexisting variants. The drugs 8-azaguaine (AG) and 6-thioguanine (TG) were used and, as a parameter for resistance, the incorporation of hypoxanthine was determined. Preexisting variation among clones in the uptake of hypoxanthine was found, and this variation has a hereditary component. This transmission of aberrant incorporation of hypoxanthine does not appear a stable trait, and the aberrant cell lines returned gradually to the original steady state. There are indications that within a cell population cells with altered levels of incorporation of hypoxanthine arise continuously and at a high frequency. Treatment with marginally toxic concentrations of AG or TG indicates that, at least for AG, survival is not related to the preexisting variation in hypoxanthine uptake. The observed phenomena could be of importance for the selection of drugs to be used in cancer chemotherapy.
当哺乳动物细胞在低浓度有毒药物中培养时，它们常常会出现表型抗性。我们研究了这种表型抗性是否是由于对预先存在的变异体进行选择所致。使用了8-氮杂鸟嘌呤（AG）和6-硫鸟嘌呤（TG）这两种药物，并将次黄嘌呤的掺入作为抗性参数进行测定。发现克隆之间在次黄嘌呤摄取方面存在预先存在的变异，且这种变异具有遗传成分。次黄嘌呤异常掺入的这种传递似乎不是一个稳定的性状，异常细胞系会逐渐恢复到原始稳态。有迹象表明，在细胞群体中，次黄嘌呤掺入水平改变的细胞会持续且高频地出现。用略有毒性浓度的AG或TG处理表明，至少对于AG来说，细胞存活与预先存在的次黄嘌呤摄取变异无关。观察到的这些现象对于癌症化疗中所用药物的选择可能具有重要意义。
