Inhibitors of poly(ADP-ribose) synthesis enhance X-ray killing of log-phase Chinese hamster cells.
Postirradiation incubation of V79 Chinese hamster cells with inhibitors of poly(ADP-ribose) synthesis was found to potentiate the killing of cells by X rays. Potentiation increased with incubation time and with concentration of the inhibitor. Preirradiation incubation had only a small effect. The enhanced response correlated well with the known extent of the inhibition of poly(ADP-ribose) synthesis. A radiation-sensitive line, V79- AL162 /S-10, was affected to a lesser extent than the normal cells. Cells repaired the radiation damage with which the inhibitors interacted within 1 hr, a process that has similar kinetics to what is observed when a postirradiation treatment with hypertonic buffer is used [H. Utsumi and M. M. Elkind , Radiat . Res. 77, 346-360 (1979)]. However, the sectors of damage affected by inhibitors of poly(ADP-ribose) synthesis and hypertonic buffer do not entirely overlap. The inhibitor nicotinamide enhanced the killing mainly of late S-phase cells and did not affect cells at the G1/S border. It is concluded that the repair process(es) involving poly(ADP-ribose) synthesis is important for cell survival in repair-competent cells and that the radiation-sensitive cells that were examined are partially deficient in a repair pathway in which poly(ADP-ribose) participates.
D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects*; D006224:Cricetinae; D003412:Cricetulus; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D009702:Nucleoside Diphosphate Sugars / Q000096:biosynthesis*; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors*; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis*; D011065:Poly(ADP-ribose) Polymerases; D011718:Pyrazinamide / Q000494:pharmacology; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D062367:ortho-Aminobenzoates / Q000494:pharmacology; D062366:para-Aminobenzoates
D001549:Benzamides; D009702:Nucleoside Diphosphate Sugars; D011838:Radiation-Sensitizing Agents; D062367:ortho-Aminobenzoates; D062366:para-Aminobenzoates; D009536:Niacinamide; D011064:Poly Adenosine Diphosphate Ribose; D011718:Pyrazinamide; C037689:benzamide; C041338:4-aminobenzamide; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases; D009713:Nucleotidyltransferases; C000219:anthranilamide; D010129:4-Aminobenzoic Acid; C008472:N-methylnicotinamide