The cell-cycle dependent and the DNA-damaging agent-induced changes of cellular NAD content and their significance.
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.
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity; D001549:Benzamides / Q000633:toxicity; D002453:Cell Cycle; D002460:Cell Line; D004249:DNA Damage; D004261:DNA Replication; D006801:Humans; D007399:Interphase; D008741:Methyl Methanesulfonate / Q000633:toxicity; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D009243:NAD / Q000378:metabolism*; D009536:Niacinamide / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009243:NAD; D008769:Methylnitronitrosoguanidine; D009536:Niacinamide; D015112:4-Nitroquinoline-1-oxide; C025160:3-aminobenzamide; D008741:Methyl Methanesulfonate; D011065:Poly(ADP-ribose) Polymerases