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.
Sugiyama
M
M
Department of Medical Biochemistry, Kurume University School of Medicine, Japan.
Costa
M
M
Nakagawa
T
T
Hidaka
T
T
Ogura
R
R
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002478:Cells, Cultured; D002840:Chromates / Q000494:pharmacology*; D006224:Cricetinae; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D009702:Nucleoside Diphosphate Sugars / Q000096:biosynthesis*; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis*; D017670:Sodium Compounds
D001549:Benzamides; D002840:Chromates; D009702:Nucleoside Diphosphate Sugars; D017670:Sodium Compounds; D011064:Poly Adenosine Diphosphate Ribose; C028982:sodium chromate(VI); C025160:3-aminobenzamide; D008741:Methyl Methanesulfonate