Exp Mol Med.  1998 Dec;30(4):186-191.

Enhancement of aflatoxin B1-induced enzyme altered hepatic foci in rats by treatment with carbon tetrachloride

• Qin G
• Ning Y
• Su J
• Shinozuka
• Lotlikar P

Abstract

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.

Keyword

Hepatocarcinogenesis; Aflatoxin B1; Carbon tetrachloride; Enzyme altered foci

MeSH Terms

Aflatoxin B1/pharmacology*
Animal
Carbon Tetrachloride/pharmacology*
Drug Synergism
Fibrosis/chemically induced
Glutathione Transferase/metabolism*
Immunohistochemistry
Lipid Peroxidation/drug effects
Liver Neoplasms, Experimental/chemically induced*
Male
Rats
gamma-Glutamyltransferase/metabolism*