Inhibitors of poly(ADP-ribose) polymerase enhance DNA strand breaks, excision repair, and sister chromatid exchanges induced by alkylating agents.
Benzamide and 3-aminobenzamide, inhibitors of poly(ADP-ribose) polymerase, synergistically enhanced the frequencies of unscheduled DNA synthesis and sister chromatid exchanges in Chinese hamster ovary (CHO) cells treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). These inhibitors also increased methyl methanesulfonate (MMS)- or MNNG-induced DNA strand breaks and significantly retarded the rejoining of strand breaks in CHO and HeLa S3 cells. These results suggest that poly(ADP-ribose) is important in the repair of DNA damage after exposure to alkylating agents and exercises a regulatory role in stabilizing chromatin structure whenever strand breaks occur in DNA.
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D001549:Benzamides / Q000633:toxicity*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003434:Crossing Over, Genetic / Q000187:drug effects*; D004247:DNA / Q000302:isolation & purification / Q000378:metabolism; D004260:DNA Repair / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D007700:Kinetics; D009153:Mutagens / Q000633:toxicity*; D009244:NAD+ Nucleosidase / Q000037:antagonists & inhibitors*; D010053:Ovary; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D000477:Alkylating Agents; D001549:Benzamides; D009153:Mutagens; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C037689:benzamide; C025160:3-aminobenzamide; D004247:DNA; D009244:NAD+ Nucleosidase