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.
Milo
G E
GE
Kurian
P
P
Kirsten
E
E
Kun
E
E
D000081:Acetamides / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D002273:Carcinogens; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects*; D003374:Coumarins / Q000494:pharmacology; D005347:Fibroblasts / Q000201:enzymology*; D006801:Humans; D009244:NAD+ Nucleosidase / Q000037:antagonists & inhibitors*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011794:Quercetin / Q000494:pharmacology
D000081:Acetamides; D000900:Anti-Bacterial Agents; D001549:Benzamides; D002273:Carcinogens; D003374:Coumarins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D002083:Butylated Hydroxyanisole; D011794:Quercetin; C030123:coumarin; D009244:NAD+ Nucleosidase; C014026:hexamethylene bisacetamide