Involvement of poly (ADP-ribose) in the radiation response of mammalian cells.
The evidence implicating poly (ADP-ribose) in the radiation response of mammalian cells is reviewed. It is concluded that the apparently conflicting results using inhibitors of ADP-ribosyl transferase (ADPRT) can be explained by a working hypothesis. This hypothesis maintains that poly (ADP-ribose) is required for repair of radiation damage (presumably to facilitate ligation). In most cells the synthesis of poly (ADP-ribose) is not rate limiting for repair and therefore, an almost complete inhibition of ADPRT activity is required to potentiate the radiation response. In radiation-sensitive cells (e.g. resting lymphocytes, L5178Y-S cells) with a deficient poly (ADP-ribose) metabolism, its synthesis can become rate limiting for repair. In such cells even a partial inhibition of ADPRT activity may enhance radiation-induced cell killing. It is suggested that if such differences exist between normal and cancer cells, they can be utilized to improve the therapeutic ratio of radiotherapy.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001761:Bleomycin / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000528:radiation effects*; D004260:DNA Repair / Q000187:drug effects; D004273:DNA, Neoplasm / Q000528:radiation effects; D006801:Humans; D007940:Leukemia L5178 / Q000473:pathology; D008213:Lymphocyte Activation / Q000528:radiation effects; D051379:Mice; D009702:Nucleoside Diphosphate Sugars / Q000378:metabolism*; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases
D001549:Benzamides; D004273:DNA, Neoplasm; D009702:Nucleoside Diphosphate Sugars; D001761:Bleomycin; D011064:Poly Adenosine Diphosphate Ribose; C037689:benzamide; C025160:3-aminobenzamide; D004247:DNA; D011065:Poly(ADP-ribose) Polymerases; D009713:Nucleotidyltransferases