Radiation damage repair capacity of a human germ-cell tumour cell line: inhibition by 3-aminobenzamide.
The capacity of a human germ-cell tumour line to repair radiation damage has been investigated by means of a clonogenic assay. Dose-rate dependence studies, split-dose experiments and experiments designed to measure repair of potentially lethal damage have been performed. The cells showed some ability to repair radiation-induced damage in all three types of experiment. An attempt has been made to understand the possible cellular mechanisms of these repair processes by the use of 3-aminobenzamide (3-AB), an agent thought to act by inhibition of ADP-ribosylation. 3-AB added 2 h prior to and removed 18 h after irradiation at a non-toxic dose to unirradiated cells caused a small but consistent increase in cell kill with acute (150 cGy min-1) irradiation, largely involving a reduction in the shoulder region of the survival curve, but had a greater effect in increasing cell kill at a dose rate of 7.6 cGy min-1 and an even greater effect at a dose rate of 1.6 cGy min-1. When 3-Ab was present 2 h prior to the first dose and between two equal doses in a split-dose experiment, inhibition of split-dose recovery was observed. In addition, some inhibition of potentially lethal damage recovery was observed with 3-AB. A possible role for poly(ADP-ribosylation) is thus implicated in the repair of radiation-induced damage of this human tumour cell line during continuous low dose rate or fractionated radiation schedules, although other effects of 3-AB on respiratory metabolism and/or purine synthesis cannot be eliminated as the cause of the observed inhibitory effects.
D001549:Benzamides / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D004247:DNA / Q000528:radiation effects*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007700:Kinetics; D011064:Poly Adenosine Diphosphate Ribose / Q000502:physiology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011064:Poly Adenosine Diphosphate Ribose; C025160:3-aminobenzamide; D004247:DNA