The Effect of Dehydroepiandrosterone on Inhibition of Carcinogenesis and Induction of Apoptosis in Murine Hepatoma Model

ABSTRACT

Tumor suppressive effect of dehydroepiandrosterone (DHEA) on the experimentally induced hepatocellular carcinoma was investigated, especially focusing on glutatione transferase and transglutaminase with aptosis in the carcinogenesis. The chemical hepatocarcinogenic procedure of Solt-Farber method was used on Sprague-Dawley rats. Experimental groups were divided into AA group treated by the standard Solt-Farber regimen of diethylnitrosamine (DEN) and 2-acetamidofluorene (AAF) and AD group treated with DHEA simultaneously with AAF and the AAD group treated by DHEA after treatment with AAF. Each group was divided by time sequence further into four subgroups, GI (8wk), G2 (16wk), G3 (28wk), and G4 (36wk). For neoplastic lesion, the immuno histochemical study with anti GSTP antibody was carried out, while the activity and expression of TGase was compared at the same time. The results were summarized as follows; GST-P positive foci detected in AD groups were significantly more suppressed by DHEA treatment than AA groups (P<0.05). AD groups. AD group showed higher activities of TGase than AA groups (P<0.05), which was confirmed by Western and Northern blot analysis. But the number of apoptotic bodies was not correlated with activity and expression of TGase in the nodule. These results suggest that the suppressive effect of DHEA on the murine hepatocellular carcinogenesis might be operating on the promotion process of carcinogenesis rather than regression process of transformed hyperplastic nodules.