Phenotypic modulation of hepatocarcinogenesis and reduction in N-nitrosomorpholine-induced hemangiosarcoma and adrenal lesion development in Sprague-Dawley rats by dehydroepiandrosterone.

Dietary administration of 0.25% dehydroepiandrosterone (DHEA) during and subsequent to 7 weeks treatment with N-nitrosomorpholine (NNM) resulted in significantly reduced development of adrenal cortical lesions and hemangiosarcomas in the liver. In addition, distinct phenotypic modulation of hepatocellular tumours was observed after combined hormone and carcinogen treatment. Thus the neoplasms were characterized by a higher degree of differentiation, lower mitotic rate and reduced potential for metastasis as compared to tumours observed after NNM alone. The data clearly indicate that DHEA exerts an inhibitory effect on both adrenal and hepatocarcinogenesis similar to that earlier reported for neoplasia in lung, thyroid, colon and skin.