Enhancement of aflatoxin B1-induced enzyme altered hepatic foci in rats by treatment with carbon tetrachloride.
- Author:
Guozhong QIN
1
;
Yaoyu NING
;
Jianjia SU
;
Hisashi SHINOZUKA
;
Prabhakar D LOTLIKAR
Author Information
1. Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
- Publication Type:Original Article ; Research Support, U.S. Gov't, P.H.S.
- Keywords:
Hepatocarcinogenesis;
Aflatoxin B1;
Carbon tetrachloride;
Enzyme altered foci
- MeSH:
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*
- From:Experimental & Molecular Medicine
1998;30(4):186-191
- CountryRepublic of Korea
- Language:English
-
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.
