Inhibition of Carcinogen-Induced Cellular Transformation of Human Fibroblasts by Drugs that Interact with the Poly(ADP-Ribose) Polymerase System

摘要

Two types of interactions of 13 drugs with human fibroblasts were determined: (a) I sub 50 of nuclear poly(ADP-ribose) polymerase,as assayed with isolated nuclei in vitro, and (b) the nontoxic concentration of drugs that prevented carcinogen-induced cell transformation of intact fibroblasts RCF sub 1). In general, RCF sub 1 was much lower than I sub 50, 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.