Antagonistic action of a tumor promoter and a poly(adenosine diphosphoribose) synthesis inhibitor in radiation-induced transformation in vitro.
Transformation of mouse C3H 10T1/2 cells by X-irradiation in vitro was blocked by the addition of 1 mM 3-aminobenzamide, an inhibitor of polyadenosine diphosphoribose (poly[ADP-ribose]) synthesis immediately after irradiation. 3-Aminobenzamide also inhibited an increase in the frequency of transformants caused by the addition of the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate, 7 days after irradiation. These results demonstrate a role for poly(ADP-ribose) synthesis during the initiation and promotion stages of transformation. From previous studies it is known that poly(ADP-ribose) synthesis is stimulated by the DNA damage caused by X rays during initiation. During promotion, however, 12-O-tetradecanoylphorbol-13-acetate acted as a mitogen but did not induce detectable DNA damage, and we could detect no stimulation of poly(ADP-ribose) synthetase. The roles of poly(ADP-ribose) during initiation and during promotion must, therefore, be significantly different.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000528:radiation effects; D002999:Clone Cells; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005347:Fibroblasts / Q000528:radiation effects; D051379:Mice; D008809:Mice, Inbred C3H; D009702:Nucleoside Diphosphate Sugars / Q000096:biosynthesis*; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology
D001549:Benzamides; D002273:Carcinogens; D004273:DNA, Neoplasm; D009702:Nucleoside Diphosphate Sugars; D011064:Poly Adenosine Diphosphate Ribose; C025160:3-aminobenzamide; D013755:Tetradecanoylphorbol Acetate