Tlsty T D, Brown P C, Schimke R T
Mol Cell Biol. 1984 Jun;4(6):1050-6. doi: 10.1128/mcb.4.6.1050-1056.1984.
Pretreatment of 3T6 murine cells with the carcinogen UV radiation or N-acetoxy-N-acetylaminofluorene increased the number of methotrexate-resistant colonies. This carcinogen-induced enhancement was seen only at low toxicities. The enhancement was transient and was observed at its maximum when cells were subjected to methotrexate selection 12 to 24 h after treatment. The addition of a tumor-promoting agent, 12-O-tetradecanoylphorbol-13-acetate, during or after carcinogen treatment further enhanced this effect. A large proportion of the resistant colonies had an increase in the dihydrofolate reductase gene copy number and the relative proportions of colonies with amplified genes were similar, regardless of whether selected cells were untreated, treated with carcinogen, or treated with carcinogen plus promoter. We discuss some of the variables which both enhance the generation and improve the detection of methotrexate-resistant colonies, as well as certain implications of our results for the generation and mechanism of gene amplification.
用致癌物紫外线辐射或N-乙酰氧基-N-乙酰氨基芴对3T6小鼠细胞进行预处理，可增加耐甲氨蝶呤集落的数量。这种致癌物诱导的增强作用仅在低毒性时可见。这种增强是短暂的，在处理后12至24小时对细胞进行甲氨蝶呤选择时观察到其最大值。在致癌物处理期间或之后添加肿瘤促进剂12-O-十四酰佛波醇-13-乙酸酯可进一步增强这种效应。很大一部分抗性集落的二氢叶酸还原酶基因拷贝数增加，并且无论选择的细胞是未处理的、用致癌物处理的还是用致癌物加启动子处理的，具有扩增基因的集落的相对比例都是相似的。我们讨论了一些既增强耐甲氨蝶呤集落的产生又改善其检测的变量，以及我们的结果对基因扩增的产生和机制的某些影响。
