Enhancement of aflatoxin B1-induced enzyme altered hepatic foci in rats by treatment with carbon tetrachloride.
The effect of carbon tetrachloride (CCl4) on aflatoxin B1 (AFB1)-induced enzyme altered hepatic foci has been examined in young male Fischer rats given AIN-76A diet. A single i.p. dose of AFB1 (0.2 mg/kg body wt) was given to rats 24 h after partial hepatectomy. Two weeks later, CCl4 (0.8 ml/kg body wt) was injected i.p. once a week for 9 weeks. Animals were sacrificed 24 h after the last dose of CCl4 and glutathione S-transferase placental form (GST-P) and gamma-glutamyl transpeptidase (GGT) positive hepatic foci were analyzed by immunohistochemical and histochemical methods, respectively. Ten weeks after AFB1 dosing, treatment with CCl4 increased the number of AFB1-induced enzyme altered foci several fold and produced a ten to twenty-fold increase in area and volume. GST-P was more sensitive than GGT in detecting AFB1-induced enzyme altered foci. Treatment with AFB1 or CCl4 produced mild hepatic fibrosis in zones 1 and 3 respectively, whereas both treatments produced severe fibrosis in zones 1 to 3 areas. Treatment with CCl4 after AFB1 dosing lowered hepatic GSH levels by 20% and increased lipid peroxidation by 40%. It appears that CCl4, by being an effective enhancer of AFB1-induced enzyme altered hepatic foci in the rat, may mimic cirrhosis observed in human hepatocellular carcinoma.
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Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Ning
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Su
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Shinozuka
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Lotlikar
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D016604:Aflatoxin B1 / Q000494:pharmacology*; D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D004357:Drug Synergism; D005355:Fibrosis / Q000139:chemically induced; D005982:Glutathione Transferase / Q000378:metabolism*; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D051381:Rats; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D016604:Aflatoxin B1; D002251:Carbon Tetrachloride; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase