Inhibition of X-ray- and ultraviolet light-induced transformation in vitro by modifiers of poly(ADP-ribose) synthesis.
Neoplastic transformation in vitro of hamster embryo cells and mouse C3H 10T1/2 cells by X rays and ultraviolet light was suppressed by benzamide or 3-aminobenzamide, agents which inhibit poly(ADP-ribose) polymerization. Suppression was observed under conditions in which the inhibitors reduce poly(ADP-ribose) polymerization by about 75% and increase sister chromatid exchange frequencies, but have no influence on repair of X-ray and uv damage and reportedly have no detectable side effects on nucleotide precursor metabolism. These findings suggest that the mechanisms regulating neoplastic transformation differ from those regulating mutagenesis and sister chromatid exchanges and are mediated via alterations in poly(ADP-ribosylation), causing changes in gene control and expression.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000528:radiation effects*; D002478:Cells, Cultured; D006224:Cricetinae; D004260:DNA Repair; D008647:Mesocricetus; D051379:Mice; D008809:Mice, Inbred C3H; D009702:Nucleoside Diphosphate Sugars / Q000096:biosynthesis*; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis*; D012854:Sister Chromatid Exchange; D014466:Ultraviolet Rays; D014965:X-Rays
D001549:Benzamides; D009702:Nucleoside Diphosphate Sugars; D011064:Poly Adenosine Diphosphate Ribose; C037689:benzamide; C025160:3-aminobenzamide