Inhibition of carcinogen-induced cellular transformation of human fibroblasts by drugs that interact with the poly(ADP-ribose) polymerase system. Initial evidence for the development of transformation resistance.

Two types of interactions of 13 drugs with human fibroblasts were determined: I50 of nuclear poly(ADP-ribose) polymerase, as assayed with isolated nuclei in vitro, and the non-toxic concentration of drugs that prevented carcinogen-induced cell transformation of intact fibroblasts (RCF1). In general, RCF1 was much lower than I50, and one antitransformer did not inhibit the enzyme in vitro, indicating that low-affinity enzyme inhibitory sites appear to play no role in the mechanism of prevention of cell transformation. Two enzyme inhibitors, caffeine and 1-methylnicotinamide, exhibited no antitransforming activity. Benzamide when applied in population doubling 1 induced resistance to cell transformation in population doubling 6 by carcinogens added at this stage.