Involvement of DNA polymerases in the repair of DNA damage by benzo[a]pyrene in cultured Chinese hamster cells.
Mechanisms for induction of single-strand scissions in DNA by S9-activated benzo[a]pyrene (B[a]P) and their repair in cultured Chinese hamster V79 cells were investigated with inhibitors of DNA-repair synthesis using alkaline sucrose gradient sedimentation analysis. The marked induction of single-strand scissions in DNA was observed following 3 h treatment of V79 cells with 5 micrograms/ml of B[a]P. These DNA lesions were repaired to the control level within 4 h after removal of B[a]P. The simultaneous addition of inhibitors of DNA-repair synthesis. 1-beta-D-arabinofuranosylcytosine (araC) plus hydroxyurea with B[a]P did not increase the formation of DNA single-strand scissions. When these inhibitors were added after removal of B[a]P, however, they significantly blocked the rejoining of DNA-strand scissions. On the other hand, when aphidicolin, a specific inhibitor of DNA polymerase alpha, was used instead of araC, a partial inhibition of the rejoining was observed, and further addition of 2',3'-dideoxythymidine, an inhibitor of DNA polymerase beta, augmented the inhibitory effect. These results indicate that B[a]P-induced single-strand scissions of DNA in V79 cells could be repaired mostly by excision repair which involved DNA polymerase alpha and a non-alpha polymerase, presumably polymerase beta.
D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001711:Biotransformation; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003561:Cytarabine / Q000494:pharmacology; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D006918:Hydroxyurea / Q000494:pharmacology; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats
D003561:Cytarabine; D001564:Benzo(a)pyrene; D004259:DNA-Directed DNA Polymerase; D006918:Hydroxyurea