Iseki S, Mori T
Cancer Res. 1985 Sep;45(9):4224-8.
The antitumor antibiotic neocarzinostatin (NCS), which produces single-strand breaks in mammalian cell DNA in vivo, stimulated the activity of chromatin bound enzyme, poly(ADP-ribose) polymerase in HeLa-S3 cells. Because of the possible causal relationship between the poly ADP-ribosylation of chromatin protein and NCS-induced temporary G2 arrest in the cell cycle, several classes of inhibitors of poly(ADP-ribose) polymerase were examined to evaluate the effect on NCS-induced polymerase activity as well as on progression in the cell cycle of synchronized HeLa cells which had been treated with NCS in G2. Compared at the same concentration of 2 mM, the polymerase-inhibiting activity was larger in the order of thymidine, 3-aminobenzamide, nicotinamide, theophylline, and caffeine. Among these agents, caffeine, theophylline, and thymidine caused a reduction in the G2 delay in this order by stimulating the cells to undergo mitosis after NCS treatment. However, 3-aminobenzamide and nicotinamide were poor reducers, if any, of NCS-induced G2 delay. These results suggest that there is not a direct involvement of poly ADP-ribosylation of chromatin protein in the mechanism of NCS-induced G2 delay. The effect of caffeine on G2 delay will probably be independent of its activity as a poly(ADP-ribose) polymerase inhibitor.
抗肿瘤抗生素新制癌菌素（NCS）能在体内使哺乳动物细胞DNA产生单链断裂，它可刺激HeLa-S3细胞中与染色质结合的酶——聚（ADP-核糖）聚合酶的活性。鉴于染色质蛋白的聚ADP-核糖基化与NCS诱导的细胞周期中暂时的G2期阻滞之间可能存在因果关系，研究了几类聚（ADP-核糖）聚合酶抑制剂，以评估其对NCS诱导的聚合酶活性以及对在G2期用NCS处理过的同步化HeLa细胞的细胞周期进程的影响。在相同浓度2 mM下比较，聚合酶抑制活性大小依次为胸苷、3-氨基苯甲酰胺、烟酰胺、茶碱和咖啡因。在这些试剂中，咖啡因、茶碱和胸苷通过刺激细胞在NCS处理后进行有丝分裂，依次导致G2期延迟缩短。然而，3-氨基苯甲酰胺和烟酰胺对NCS诱导的G2期延迟的缩短作用（如果有的话）很差。这些结果表明，染色质蛋白的聚ADP-核糖基化在NCS诱导的G2期延迟机制中并非直接参与。咖啡因对G2期延迟的影响可能与其作为聚（ADP-核糖）聚合酶抑制剂的活性无关。
