Possible enhancing effect of the immunosuppressive agent, 6-mercaptopurine(6-MP) on focal lesion development in cirrhotic liver induced by carbon tetrachloride but not furfural in F344 rats

The modifying effects of an immunosuppressive agent, 6-mercaptopurine (6-MP), on development of focal lesions in liver cirrhosis models induced by carbon tetrachloride (CCl4) or furfural were studied in male F344 rats. Feeding of 6-MP at 50 p.p.m. for 20 weeks to animals with pre-existing liver cirr...

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Published inCarcinogenesis (New York) Vol. 13; no. 8; p. 1365
Main Authors Maruyama, H, Amanuma, T, Takashima, Y, Yoshiji, H, Nakae, D, Tsutsumi, M, Tsujiuchi, T, Denda, A, Konishi, Y
Format Journal Article
LanguageEnglish
Published England 01.08.1992
Subjects
Alkaline Phosphatase - analysis
Animals
Aspartate Aminotransferases - analysis
Carbon Tetrachloride
Drug Synergism
Furaldehyde
gamma-Glutamyltransferase - analysis
Glutathione Transferase - analysis
Liver - drug effects
Liver - enzymology
Liver Cirrhosis, Experimental - chemically induced
Liver Cirrhosis, Experimental - enzymology
Liver Cirrhosis, Experimental - pathology
Liver Neoplasms - chemically induced
Male
Mercaptopurine - adverse effects
Phenobarbital - pharmacology
Precancerous Conditions - chemically induced
Rats
Rats, Inbred F344
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Summary:The modifying effects of an immunosuppressive agent, 6-mercaptopurine (6-MP), on development of focal lesions in liver cirrhosis models induced by carbon tetrachloride (CCl4) or furfural were studied in male F344 rats. Feeding of 6-MP at 50 p.p.m. for 20 weeks to animals with pre-existing liver cirrhosis caused immunosuppression, and significantly enhanced the induction of gamma-glutamyltranspeptidase (GGT)-positive foci and nodules in the CCl4 but not furfural case. Glutathione S-transferase P (GST-P)-positive preneoplastic lesions were not affected. Moreover, phenobarbital (PB) also enhanced the induction of GGT-positive hepatocellular lesions only in the CCl4-induced liver cirrhosis model, no promotion influence being exerted after treatment with the non-carcinogenic furfural. This study, therefore, suggests that 6-MP can enhance the induction of one type of preneoplastic foci and nodules and that essential differences exist between focal lesions arising in cirrhotic livers caused by CCl4 as opposed to furfural.
ISSN:0143-3334
DOI:10.1093/carcin/13.8.1365