Newman C N, Miller J H
Biochem Biophys Res Commun. 1983 Jul 18;114(1):34-40. doi: 10.1016/0006-291x(83)91590-5.
Deoxynucleoside triphosphate concentrations in Chinese hamster ovary cell lines, CHO-K1 and Mut 8-16, were examined following exposure of cells to UV or dimethylsulfate. Marked decreases in dCTP were observed 2 hr after exposure to both mutagens. In contrast, dTTP concentrations increased with increased cell killing after exposure to UV but not after exposure to dimethylsulfate. Examination of DNA synthesis in permeabilized cells in the presence of excess concentrations of dNTP substrates suggests that excess dCTP enhances replication while excess of dTTP inhibits replication. We therefore ask whether the increase in the dTTP/dCTP ration in mutagenized whole cells either contributes to or prolongs induced inhibition of replication. In addition we proposed that such an induced dNTP imbalance may also contribute to an increase in mutations by enhancing the probability for base-misincorporation.
在用紫外线或硫酸二甲酯处理中国仓鼠卵巢细胞系CHO-K1和Mut 8-16后,检测了细胞中的脱氧核苷三磷酸浓度。暴露于这两种诱变剂后2小时,观察到dCTP显著降低。相比之下,紫外线照射后,dTTP浓度随细胞杀伤增加而升高,但硫酸二甲酯处理后则不然。在存在过量dNTP底物的情况下,对通透细胞中的DNA合成进行检测表明,过量的dCTP会增强复制,而过量的dTTP则会抑制复制。因此,我们提出疑问,诱变处理的完整细胞中dTTP/dCTP比值的增加是否会导致或延长诱导的复制抑制。此外,我们还提出,这种诱导的dNTP失衡可能还会通过增加碱基错配的概率而导致突变增加。