Wilkinson Y A, McKenna P G
Biomedical Sciences Research Centre, University of Ulster, Coleraine, Northern Ireland.
Leuk Res. 1989;13(7):615-20. doi: 10.1016/0145-2126(89)90130-6.
The ability of excess thymidine (10(-6)-10(-3) M) to enhance the frequency of 6-thioguanine (6-TG) resistant cell mutants and 2,6-diaminopurine (DAP) resistant cell mutants in Friend mouse erythroleukaemia cells, clone 707, was investigated. A significant increase in mutant frequency for both markers was observed at the higher (10(-4) and 10(-3) M) thymidine treatments. Measurements of deoxyribonucleoside triphosphate pool sizes in the cells revealed a dramatic elevation of the deoxythymidine triphosphate and deoxyguanosine triphosphate pools, an increase in the deoxyadenosine triphosphate pool and an almost complete disappearance of the deoxycytidine triphosphate pool at the higher thymidine treatments. This complemented the mutagenesis data. These results support the view that increases in mutant frequency may take place following perturbations in DNA precursor pools through a resultant decrease in the fidelity of DNA synthesis. Measurements of deoxyribonucleoside triphosphate pools were also carried out on clone 707 Friend cells and a thymidine kinase-deficient subclone, 707 BUF. The thymidine kinase-deficient subclone had significantly reduced deoxythymidine triphosphate and deoxyguanosine triphosphate pools relative to those observed in-clone 707 cells. The previously observed mutagen hypersensitivity in thymidine kinase-deficient Friend cells may result through pool imbalance rendering DNA excision repair error prone.
研究了过量胸苷（10⁻⁶ - 10⁻³ M）提高弗氏小鼠红白血病细胞系707中6-硫鸟嘌呤（6-TG）抗性细胞突变体和2,6-二氨基嘌呤（DAP）抗性细胞突变体频率的能力。在较高浓度（10⁻⁴和10⁻³ M）的胸苷处理下，观察到两种标记物的突变频率均显著增加。对细胞中脱氧核糖核苷三磷酸池大小的测量显示，在较高的胸苷处理下，脱氧胸苷三磷酸和脱氧鸟苷三磷酸池显著升高，脱氧腺苷三磷酸池增加，而脱氧胞苷三磷酸池几乎完全消失。这与诱变数据相吻合。这些结果支持这样一种观点，即DNA前体池受到干扰后，可能会因DNA合成保真度的降低而导致突变频率增加。还对707弗氏细胞系及其胸苷激酶缺陷亚克隆707 BUF进行了脱氧核糖核苷三磷酸池的测量。与707细胞系相比，胸苷激酶缺陷亚克隆的脱氧胸苷三磷酸和脱氧鸟苷三磷酸池显著减少。先前在胸苷激酶缺陷的弗氏细胞中观察到的诱变超敏性可能是由于池失衡导致DNA切除修复容易出错所致。
