Tumor-promoting barbiturates act on DNA repair of cultured hepatocytes.
We have observed that two promoters of liver carcinogenesis, i.e. phenobarbital and barbital, markedly increase DNA-repair synthesis of cultured hepatocytes following treatment with the ultimate carcinogens methyl methanesulfonate, N-methyl-N'-nitro-N-nitrosoguanidine, N-acetoxy-2-acetylaminofluorene, and UV light of 254 nm. Phenobarbital also increased the incorporation rates of deoxynucleoside triphosphates into nuclear DNA of permeabilized hepatocytes following carcinogen treatment. The action of these barbiturates apparently correlates with their potential to promote hepatocarcinogenesis in vivo, since the non-promoting agent barbituric acid did not modify carcinogen-induced repair synthesis. Moreover, the mechanisms of action of tumor-promoting barbiturates is different from the known enhancing action on repair synthesis of inhibitors of nuclear poly(ADP-ribose) biosynthesis.
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D062365:Aminobenzoates / Q000494:pharmacology; D000818:Animals; D001462:Barbital / Q000494:pharmacology; D001463:Barbiturates / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair / Q000187:drug effects*; D008099:Liver / Q000166:cytology; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D009713:Nucleotidyltransferases / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases; D051381:Rats
D062365:Aminobenzoates; D001463:Barbiturates; D001549:Benzamides; D002273:Carcinogens; D000246:Adenosine Diphosphate Ribose; D001462:Barbital; C025160:3-aminobenzamide; D004247:DNA; D008741:Methyl Methanesulfonate; D011065:Poly(ADP-ribose) Polymerases; D009713:Nucleotidyltransferases; D010634:Phenobarbital