Das S K, Berger N A
Biochem Biophys Res Commun. 1986 Jun 30;137(3):1153-8. doi: 10.1016/0006-291x(86)90346-3.
Treatment of L1210 cells with increasing concentrations of MNNG produces heterogeneous perturbations of cellular deoxynucleoside triphosphate pools, with the magnitude and direction of the shift depending on the deoxynucleotide and on the concentration and time of exposure of the DNA damaging agent. 5 microM MNNG stimulated an increase in dATP, dCTP and dTTP but dGTP pools remained constant. These increases were not affected by 3-aminobenzamide, indicating that the pool size increases were produced by poly(ADP-ribose) polymerase independent reactions. 30 microM MNNG caused a time dependent decrease in dATP, dGTP, dTTP and dCTP. The dGTP pool was most drastically affected, becoming totally depleted within 3 hours. The fall in all 4 dNTP pools was substantially prevented by 3-aminobenzamide, suggesting that the decrease in dNTPs following DNA damage is mediated by a poly(ADP-ribose) polymerase dependent reaction. Severe depression of dGTP pools consequent to NAD and ATP depletion may provide a metabolic pathway for rapidly stopping DNA synthesis as a consequence of DNA damage and the activation of poly(ADP-ribose) polymerase.
用浓度递增的MNNG处理L1210细胞会产生细胞脱氧核苷三磷酸池的异质性扰动，其变化的幅度和方向取决于脱氧核苷酸以及DNA损伤剂的浓度和暴露时间。5微摩尔MNNG刺激dATP、dCTP和dTTP增加，但dGTP池保持不变。这些增加不受3-氨基苯甲酰胺的影响，表明池大小的增加是由多聚（ADP-核糖）聚合酶非依赖性反应产生的。30微摩尔MNNG导致dATP、dGTP、dTTP和dCTP随时间减少。dGTP池受影响最严重，在3小时内完全耗尽。3-氨基苯甲酰胺基本阻止了所有4种dNTP池的下降，表明DNA损伤后dNTP的减少是由多聚（ADP-核糖）聚合酶依赖性反应介导的。由于NAD和ATP耗竭导致的dGTP池严重降低可能为DNA损伤和多聚（ADP-核糖）聚合酶激活后迅速停止DNA合成提供一条代谢途径。
