Potentiation of cell killing by inhibitors of poly(ADP-ribose) polymerase in four rodent cell lines exposed to N-methyl-N-nitrosourea or UV light.
The sensitivities (Do-values) of the cytotoxic effect of MNU on four rodent cell lines were: mouse L1210, 0.07 mM; rat Yoshida sarcoma, 0.52 mM; Chinese hamster V79A, 0.70 mM and the UV sensitive, X-ray sensitive V79/79, 0.35 mM. The abilities of maximum non-toxic doses of the poly-(ADP-ribose) polymerase inhibitors, 5-methyl nicotinamide (5MeN), 3-methoxybenzamide (3MBA) and caffeine to potentiate this cytotoxicity and that of UV light in V79A and V79/79 was measured. The degree of potentiation (ratio Do without inhibitor/Do with inhibitor) was both agent and cell line dependent. In general the lymphoid cell lines L1210 and YS showed greater potentiation, up to 4-fold, than did the fibroblast lines V79A and V79/79. The use of inhibitors in pairs suggested that 5MeN and 3MBA affect one process whereas caffeine affects additional processes. The data provide further support for a role for poly(ADP-ribose) in DNA repair, but indicate that metabolic factors may modify the effectiveness of individual inhibitors of poly(ADP-ribose) polymerase in different cell lines.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D006224:Cricetinae; D004260:DNA Repair / Q000187:drug effects; D004357:Drug Synergism; D008770:Methylnitrosourea / Q000633:toxicity*; D051379:Mice; D009244:NAD+ Nucleosidase / Q000037:antagonists & inhibitors*; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D009607:Nitrosourea Compounds / Q000633:toxicity*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D051381:Rats; D014466:Ultraviolet Rays
D001549:Benzamides; D009607:Nitrosourea Compounds; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009536:Niacinamide; D002110:Caffeine; D008770:Methylnitrosourea; C024785:5-methylnicotinamide; D009244:NAD+ Nucleosidase; C025159:3-methoxybenzamide