Inhibition of DNA synthesis in mouse epidermis and breast epithelium by dehydroepiandrosterone and related steroids.

Long-term treatment of C3H mice with the adrenal steroid, dehydroepiandrosterone (DHEA), has previously been shown to suppress spontaneous breast cancer development. A single i.p. injection of DHEA into C3H or ICR mice inhibits the rate of [3H]thymidine incorporation in breast epithelium and in 12-0-tetradecanoylphorbol-13-acetate (TPA)-stimulated epidermis. DHEA is a potent non-competitive inhibitor of mammalian glucose-6-phosphate dehydrogenase (G6PDH). 16 alpha-Br-epiandrosterone (Br-Epi), which is 60 times more active than DHEA is an inhibitor of G6PDH, is also much more active in reducing the rate of [3H]thymidine incorporation into mouse breast epithelium and epidermis. Synthetically prepared DHEA-sulfatide also inhibits G6PDH activity and [3H]thymidine incorporation in TPA-stimulated mouse epidermis. On the contrary, DHEA-sulfate, which is virtually inactive as an inhibitor of G6PDH, is also inactive as an inhibitor of [3H]thymidine incorporation in mouse epidermis.