Wani M A, Strayer J M, Snapka R M
Department of Radiology, Ohio State University, Columbus 43210.
Anticancer Drugs. 1990 Oct;1(1):67-75. doi: 10.1097/00001813-199010000-00012.
Low level cytotoxic stress greatly accelerates the loss of unstably amplified dihydrofolate reductase (dhfr) genes from methotrexate-resistant mouse cell lines. To understand this drug-induced loss of amplified genes, the highly methotrexate-resistant mouse R500 cell line was flow sorted into two subpopulations with higher and lower average dhfr gene dosage respectively. The subpopulation with higher levels of gene amplification was much more sensitive to low level cytotoxic stress as judged by both cloning efficiency and growth in the presence of low concentrations of cytotoxic drugs. These results suggest that high levels of gene amplification can confer hypersensitivity to cytotoxic stressors such as anticancer drugs.
低水平的细胞毒性应激会极大地加速甲氨蝶呤抗性小鼠细胞系中不稳定扩增的二氢叶酸还原酶（dhfr）基因的丢失。为了理解这种药物诱导的扩增基因丢失现象，将高度耐甲氨蝶呤的小鼠R500细胞系通过流式细胞术分选成两个亚群，其平均dhfr基因剂量分别较高和较低。通过克隆效率和在低浓度细胞毒性药物存在下的生长情况判断，基因扩增水平较高的亚群对低水平细胞毒性应激更为敏感。这些结果表明，高水平的基因扩增可导致对细胞毒性应激源（如抗癌药物）的超敏反应。
