DNA adducts and P450 induction in human, rat and avian liver cells after exposure to polychlorobiphenyls.
Polychlorinated biphenyls (PCBs) are industrial chemicals which have been detected in fish, birds and humans. They are known to exert marked effects on the liver. They induce hepatocellular carcinoma in rats and birds, and are suspected of being carcinogenic to humans. To better understand the genotoxic effects of PCBs, we used 32P-postlabelling to investigate DNA adduct formation, after exposure to PCBs (Aroclor 1254 and 3,3',4,4'-tetrachlorobiphenyl), in primary cultures of fetal hepatocytes from two animal species and in a human cell line (Hep G2). We also studied the induction of 7-ethoxyresorufin-O-deethylase (EROD) in these PCB-treated cells. The three cell types used are known to express different cytochrome P450 families. The aim was to see whether a correlation could be established between EROD activity (a CYP1A1-related activity) and DNA adduct formation. DNA adducts were found in all three models after exposure to 50 microM 3,3',4,4'-tetrachlorobiphenyl. The number of adducts was higher in quail hepatocytes (37 adducts per 10(9) nucleotides) than in rat hepatocytes or Hep G2 cells (20 adducts per 10(9) nucleotides in both cases). The major adduct was the same in all three cell types, but some adducts were found in only one or two species. These inter-species differences probably reflect metabolic differences leading to different ultimate carcinogens. Exposure to Aroclor 1254 failed to produce significant levels of DNA adducts, suggesting that pre-treated cells are required to magnify Aroclor 1254 metabolism. No correlation was found between adduct formation and the level of EROD induction.
Dubois
M
M
Laboratoire de Chimie Medicale, Institut de Pathologie, Universite de Liege, Centre Hospitalier Universitaire, Sart-Tilman, Belgium.
Pfohl-Leszkowicz
A
A
Grosse
Y
Y
Kremers
P
P
D000704:Analysis of Variance; D000818:Animals; D001140:Aroclors / Q000633:toxicity; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002478:Cells, Cultured / Q000378:metabolism; D020111:Chlorodiphenyl (54% Chlorine); D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D018736:DNA Adducts / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D018197:Hepatoblastoma / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008113:Liver Neoplasms / Q000378:metabolism; D010088:Oxidoreductases / Q000096:biosynthesis*; D010761:Phosphorus Radioisotopes; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011784:Quail; D051381:Rats; D013045:Species Specificity; D014407:Tumor Cells, Cultured / Q000378:metabolism
D001140:Aroclors; D002274:Carcinogens, Environmental; D018736:DNA Adducts; D010761:Phosphorus Radioisotopes; D020111:Chlorodiphenyl (54% Chlorine); D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; C028451:3,4,3',4'-tetrachlorobiphenyl