Moore M M, Applegate M L, Hozier J C
Genetic Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Mutat Res. 1988 Feb;207(2):77-82. doi: 10.1016/0165-7992(88)90045-0.
TFT is an effective selective agent for TK-deficient mutants of L5178Y TK+/- -3.7.2C mouse lymphoma cells. Mutants can be classified by colony size into small colonies (many of which show readily observable chromosome abnormalities associated with chromosome 11--the location of the TK gene) and large colonies (which may represent events affecting only the expression of the TK gene). The precise nature of the induced damage causing the loss of the TK-enzyme activity for both mutant type is not known and is currently under investigation. The hypomethylating agent 5-azacytidine can be utilized to investigate the possibility that mutants might be the result of a suppressed rather than an altered TK gene. Mutant cell lines are treated with 5-azacytidine and then evaluated for re-expression of the TK enzyme as measured by resistance to THMG. In these studies, 11 mutants have been evaluated. None of the 11, including 10 small-colony mutants (6 with chromosome 11 translocations) and 1 large-colony mutant, show a high conversion to TK competency following 5-azacytidine treatment.
TFT是L5178Y TK+/- -3.7.2C小鼠淋巴瘤细胞中缺乏胸苷激酶（TK）的突变体的有效选择剂。突变体可根据集落大小分为小集落（其中许多显示出与11号染色体——TK基因所在位置相关的易于观察到的染色体异常）和大集落（这可能代表仅影响TK基因表达的事件）。导致两种突变体类型的TK酶活性丧失的诱导损伤的确切性质尚不清楚，目前正在研究中。低甲基化剂5-氮杂胞苷可用于研究突变体可能是由于TK基因被抑制而非改变的可能性。用5-氮杂胞苷处理突变细胞系，然后通过对三甲氧苄氨嘧啶（THMG）的抗性来评估TK酶的重新表达。在这些研究中，已评估了11个突变体。这11个突变体，包括10个小集落突变体（6个有11号染色体易位）和1个大集落突变体，在5-氮杂胞苷处理后均未显示出向TK活性的高转化率。
