Influence of niacin metabolism in malignant transformation in vitro

The potential role of niacin metabolism in the prevention of carcinogen-induced malignant transformation was investigated. The conversion of niacin to NAD, and its subsequent conversion to poly(ADP-ribose) was blocked by using an inhibitor of poly(ADP-ribose) or by nutritional depletion of the cellular NAD pool. Transformation frequency in exponentially dividing cells treated with the carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), was elevated 12-fold in the presence of 3-methoxybenzamide (MBA), a poly(ADP-ribose) polymerase inhibitor. A two-fold increase in transformation frequency was observed in exponentially dividing, NAD-depleted cells treated with MNNG. In contrast, the transformation frequency of confluent cultures treated with MNNG was not affected by either method of perturbing niacin metabolism. However, a significant increase in spontaneous, noninduced transformations occurred in confluent cultures when niacin metabolism was perturbed by poly(ADP-ribose) polymerase inhibitors or by niacin deprivation. These data suggest that poly(ADP-ribose) plays a critical role in recovery from DNA damage in exponentially dividing cells. Moreover, niacin metabolism may be involved in the prevention of spontaneous transformation in nondividing cells.