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.