Aroclor 1254 increases the genotoxicity of several carcinogens to liver primary cell cultures.
The genotoxicity of both direct-acting and precarcinogenic chemicals was evaluated in liver primary cell cultures (LPCC) from untreated and Aroclor 1254 (Ar) pretreated rats. Hepatocytes were isolated from partially hepatectomized rats and their DNA was labeled in vitro with [3H] dThd; the molecular weight of single-stranded DNA was determined by alkaline sucrose sedimentation. Two parameters of DNA damage were defined: the mean effective dose (ED50), i.e., the carcinogen concentration that decreased the DNA molecular weight to half the original, and the DNA breaking potency (DBP), i.e., the number of breaks per DNA molecule produced by 2 h exposure to 1 mM concentration of the chemical. Two hours exposure of LPCC from untreated rats to the direct-acting alkylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) (6.8-340 microM) and to the precarcinogens benzo[a]pyrene (BaP) (0.05-0.33 mM) and dimethylnitrosamine (DMN) (0.45-16 mM) produced a concentration-dependent decrease in the molecular weight of DNA. Pretreatment of rats with Ar decreased significantly the sedimentation velocity of DNA and increased five, three, and two times the DBP of MNNG, BaP, and DMN, respectively. These results show that Ar-pretreatment of rats increases the genotoxicity of both direct-acting and precarcinogenic chemicals and suggest that Ar might increase the genotoxicity of chemical carcinogens perhaps by enhancing their metabolic activation, by producing direct genotoxic effects, or both. Our results also emphasize the carcinogenic risk that the environmental pollution by polychlorinated biphenyls might represent to humans.
D000818:Animals; D001140:Aroclors / Q000633:toxicity*; D001564:Benzo(a)pyrene / Q000633:toxicity; D002478:Cells, Cultured; D020111:Chlorodiphenyl (54% Chlorine); D004277:DNA, Single-Stranded / Q000032:analysis; D004128:Dimethylnitrosamine / Q000633:toxicity; D004357:Drug Synergism; D008099:Liver / Q000187:drug effects*; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D008970:Molecular Weight; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D001140:Aroclors; D004277:DNA, Single-Stranded; D020111:Chlorodiphenyl (54% Chlorine); D008769:Methylnitronitrosoguanidine; D001564:Benzo(a)pyrene; D011078:Polychlorinated Biphenyls; D004128:Dimethylnitrosamine