Recent Studies on the Effect of Dehydroepiandrosterone on the Metabolism of Carcinogens in Vivo

Abstract

Dehydroepiandrosterone (DHEA), a naturally occurring adrenal steroid, has been shown to inhibit both spontaneous and chemically induced tumors in various species. The protective effects of DHEA are believed to be due to an inhibition of both the initiation and promotion phases of tumorigenesis. In our laboratories we have investigated the influence of DHEA on the metabolism and macromolecular interactions of the hepatocarcinogens NDMA, AFB₁, and the mammary carcinogen DMBA to understand some of the mechanisms involved in the inhibition of initiation of tumors by DHEA; notably metabolic activation of the carcinogens and their adduct formation with hepatic DNA. Binding of these carcinogens to hepatic DNA was significantly inhibited in the steroid-fed rats. However, the binding of these carcinogens to total liver protein was 2-3 fold higher in the DHEA-fed rats. In vivo and in vitro metabolic studies suggested that DHEA enhanced the metabolic activation of these carcinogens in the liver. The implications of these results in the delineation of the molecular mechanisms involved in the anticarcinogenic action of DHEA are discussed.