Dai Y F, Yu Y N, Chen X R
Mutat Res. 1987 May;191(1):29-35. doi: 10.1016/0165-7992(87)90166-7.
NAD is the substrate of a novel chromatin-associated enzyme-ADP-ribosyl transferase (ADPRT). In this study, the cell-cycle dependent change in cellular NAD content was observed in a line of human amnion FL cells. It was found that the cellular NAD content of FL cells was highest in G1 and lowest in S/G2-G2. 3AB, a potent ADPRT inhibitor, can inhibit the cell cycle dependent change in cellular NAD content and also inhibit DNA synthesis in the S phase and extend the S phase. The results indicate that ADP-ribosylation may be involved in DNA replication and cell cycle progression. It was also found that the DNA-damaging agents, MNNG, MMS and 4NQO could lower cellular NAD content in a dose-dependent way. This DNA-damage-induced NAD lowering could be partially or completely prevented by the ADPRT inhibitors, 3AB or nicotinamide, which were shown to exert no influence on either the cellular NAD content of normal quiescent FL cells or the metabolic blocking agent, 2,4-DNP-induced cellular NAD lowering. The possibility of establishing a simple and specific method to detect DNA-damaging agents by measuring cellular NAD content in the presence or absence of ADPRT inhibitor is explored.
NAD是一种新型染色质相关酶——ADP核糖基转移酶（ADPRT）的底物。在本研究中，在人羊膜FL细胞系中观察到细胞NAD含量的细胞周期依赖性变化。发现FL细胞的细胞NAD含量在G1期最高，在S/G2-G2期最低。强效ADPRT抑制剂3AB可抑制细胞NAD含量的细胞周期依赖性变化，还可抑制S期的DNA合成并延长S期。结果表明，ADP核糖基化可能参与DNA复制和细胞周期进程。还发现DNA损伤剂MNNG、MMS和4NQO可剂量依赖性降低细胞NAD含量。ADPRT抑制剂3AB或烟酰胺可部分或完全阻止这种DNA损伤诱导的NAD降低，且这些抑制剂对正常静止FL细胞的细胞NAD含量或代谢阻断剂2,4-DNP诱导的细胞NAD降低均无影响。探讨了通过在有或无ADPRT抑制剂的情况下测量细胞NAD含量来建立一种简单、特异的检测DNA损伤剂方法的可能性。
