Stimulation of polyadenosine diphosphoribose synthesis by DNA lesions induced by sodium chromate in Chinese hamster V-79 cells.

Polyadenosine diphosphoribose [poly(ADP-ribose)] synthesis was stimulated by DNA lesions induced with Na2CrO4 and methyl methanesulfonate (MMS) in Chinese hamster V-79 cells. Na2CrO4 and MMS induced DNA single-strand breaks in a concentration-dependent manner; however, the breaks induced by Na2CrO4 were "protein associated" while those induced by MMS were not. MMS stimulated in a dose-dependent fashion the synthesis of poly(ADP-ribose) up to 6-fold above the control. Na2CrO4 also induced poly(ADP-ribose) synthesis, but the level of synthesis was less than 3-fold. Control experiments demonstrated that Na2CrO4 treatment of cells did not affect their ability to synthesize poly(ADP-ribose) in response to DNA damage. Treatment of cells with Na2CrO4 and MMS induced more poly(ADP-ribose) synthesis than each agent alone; however, whenever Na2CrO4 was utilized, the breaks required proteinase K to be detected. Following removal of extracellular chromate, the DNA strand breaks induced by 0.2 mM Na2CrO4 were repaired quickly during the first hour but more slowly for the next 3 h. In the presence of 3-aminobenzamide, an inhibitor of poly(ADP-ribose) synthesis, the repair of DNA breaks was reduced. These results suggest that DNA protein-associated breaks produced by Na2CrO4 were recognized by poly(ADP-ribose) polymerase and that there are differences in poly(ADP-ribose) synthesis in response to Na2CrO4 and MMS. The results also suggest that the repair of breaks induced by Na2CrO4 are associated with poly(ADP-ribose) synthesis, but perhaps because most of these breaks are protein associated, there is less stimulation of poly(ADP-ribose) synthesis.