Thilly W G, DeLuca J G, Hoppe H, Penman B W
Chem Biol Interact. 1976 Sep;15(1):33-50. doi: 10.1016/0009-2797(76)90126-5.
The lag in phenotype expression of methylnitrosourea(MNU)-induced mutation to 6-thioguanine (6TG) resistance has been studied in a diploid human lymphoblastoid cell line. We find that a considerable period (8-12 days) elapses before new mutants appear in treated cultures; after 2 weeks, however, a stable maximum fraction is attained, as would be expected for a genetic mutation. We present preliminary data linking this phenotypic lag to the slow degradation rate of hypoxanthine-guanine phosphoribosyl transferase (HGPRT) and to an apparent requirement for very low (less than 0.2% normal) cellular HGPRT content in order for cells to be resistant to 10 mug 6TG/ml. A series of reconstruction experiments are presented, the results of which support the conclusion that selective pressures in the assay procedure do not bias the quantitative estimates of induced mutant fraction.
在一个二倍体人淋巴母细胞系中，研究了甲基亚硝基脲（MNU）诱导的对6-硫代鸟嘌呤（6TG）抗性突变的表型表达滞后现象。我们发现，在处理后的培养物中，新突变体出现之前有相当长的一段时间（8 - 12天）；然而，2周后达到了稳定的最大比例，这与基因突变的预期情况相符。我们提供了初步数据，将这种表型滞后与次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶（HGPRT）的缓慢降解速率以及细胞对10μg 6TG/ml产生抗性时极低（低于正常水平的0.2%）的细胞HGPRT含量的明显需求联系起来。本文还展示了一系列重建实验，其结果支持这样的结论：检测过程中的选择压力不会使诱导突变体比例的定量估计产生偏差。
