Tumor suppressive effect of dehydroepiandrosterone(DHEA) on the experimentally induced hepatocellular carcinoma was illustrated, for which the molecular mechanism was studied in the aspect of cellular re#gulation of preneoplastic lesion, especially focusing on apoptosis. For the purpose, we used the murine chemical hepatocarcinogenic procedure of Solt-Farber on Sprague-Dawley rats. Experimental groups were divided into control, AA, AD and AAD groups. The AA group was the standard diethylnitrosamine(DEN) and 2-acetylaminofluorene (AAF) group, while the AD group was DHEA added group simultaneously with AAF and the AAD group was DHEA added group after the treatment with AAF. Each group was divided into nine subgroups according to the time schedule with four weeks interval after the administration of DEN. The results were analyzed by body weight, apoptotic bodies, immunohistochemical studies with anti-glutathione-S-transferase-P(GST-P) antibody and anti-TGase antibody, and biochem- ical methods. The results were summarized as follows; 1) AD and AAD groups compared with control groups showed the less increaae of body weight during DHEA treatment. 2) GST-P positive foci were detected in all subgroups, but AD groups showed the significantly decreased area of GST-P positive foci than AA groups, and this effect last to G 9(P<0.05). AAD groups showed the similar effect of decreasing. GST-P positive foci as AD groups in G 9. 3) Western blot analysis of GST-P positive foci showed comparable outcome to immunohistochemical study. 4) Anti-TGase antibody staining of apoptotic bodies(ABs) in GST-P positive foci were confirmed by pathologic and immunohistochemical studies. 5) In G 1 and G 2, AD groups showed higher activities of TGase than AA groups(P<0.05), which was confirmed by Western blot analysis using anti-TGase antibody. These results suggest that the suppressive effect of DHEA on the experimentally induced murine hepatocellular carcinoma is operating on the promotion process of carcinogenesis probably through induction of apoptosis in the Preneoplastic lesion in relation with activation of transglutaminase Rene. Words: DHEA, Apoptosis, Hepatocellular carcinoma, TGase, GST-P
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