Epiandrosterone- and dehydroepiandrosterone-3 beta-alkanesulfonates as inhibitors of mouse glucose-6-phosphate dehydrogenase activity.

3 beta-Alkanesulfonates of dehydroepiandrosterone, 16 alpha-bromodehydroepiandrosterone, epiandrosterone, and 16 alpha-bromoepiandrosterone were prepared in 54-95% yield via the reaction of long chain alkanesulfonyl chlorides with the corresponding dehydroepiandrosterone, and epiandrosterone analogues. These compounds inhibit mouse glucose-6-phosphate dehydrogenase activity.

Metabolism of NG-monomethyl-L-arginine.

Rat kidney contains an enzyme which hydrolyzes NG-monomethyl-L-arginine to give rise to the formation of ornithine and N-methylurea. Confirmation of formation of these reaction products is carried out colorimetrically as well as radiochemically employing NG-monomethyl-L-[ornithine-14C(U)]arginine. This pattern of reaction products suggests that the enzyme responsible is an arginase type. However, the kidney enzyme is quite distinct from the hepatic arginase; commercial bovine hepatic arginase (L-arginine amidinohydrolase, EC 3.5.3.1) is completely inactive toward NG-monomethyl-L-arginine. Among various rat tissues examined, the hydrolytic activity is the highest in kidney, followed by the activity in liver and pancreas.

Synthesis of dehydroepiandrosterone sulfatide and 16 alpha-halogenated steroids.

Dehydroepiandrosterone sulfatide was prepared in a 68% yield by the reaction of 5-androstene-3 beta-ol-17-one 3 sulfate (silver salt) with dipalmitoyl alpha-iodopropylene glycol. The sulfatide was found to be a more potent inhibitor of human glucose-6-phosphate dehydrogenase than dehydroepiandrosterone. 16 alpha-Halogenated steroids also were prepared by direct halogenation of the steroid or indirect halogenation of an appropriate steroidal intermediate. Among various halogenated steroids, 16 alpha-bromoepiandrosterone was 50 times as potent as dehydroepiandrosterone as an inhibitor of glucose-6-phosphate dehydrogenase.

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.

Dehydroepiandrosterone: an anti-obesity and anti-carcinogenic agent.

Long-term treatment of female C3H-Avy/A (obese) and C3H-A/A (non-obese) mice with dehydroepiandrosterone, an adrenal steroid found in subnormal levels in women predisposed to develop breast cancer, reduces weight gain without suppressing appetite and significantly inhibits the development of spontaneous breast cancer. This steroid also antagonizes the capacity of the tumor promoter, 12-0-tetradecanoyl-phorbol-13-acetate, to stimulate 3H-thymidine incorporation in mouse epidermis and in a cultured rat kidney epithelial cell line.

Dehydroepiandrosterone and 16 alpha-bromo-epiandrosterone: inhibitors of Epstein-Barr virus-induced transformation of human lymphocytes.

Dehydroepiandrosterone (DHEA), a major adrenal secretory product in men and women, is a potent inhibitor of mammalian glucose-6-phosphate dehydrogenase (G6PDH). Long-term treatment with this steroid has previously been found to suppress spontaneous breast cancer development in C3H mice. DHEA is now shown to inhibit Epstein-Barr virus (EBV)-induced morphologic transformation and stimulation of DNA synthesis in human lymphocytes. 16 alpha-Br-epiandrosterone, a DHEA analog that is about 60 times as potent as DHEA as an inhibitor of G6PDH, is much more effective as an inhibitor of EBV-induced transformation.

Accelerating effect of ascorbic acid on N-nitrosamine formation and nitrosation by oxyhyponitrite.

The reaction of nitrite ion with ascorbic acid and its effect on the rate of nitrosation of secondary amines have been investigated by differential pulse polarography in aqueous acidic solution. Ascorbic acid shows nonuniform behavior: it accelerates the nitrosation of N-methylaniline between pH 1.00 and 1.95, allows the nitrosation of diphenylamine and iminodiacetonitrile, but inhibits the nitrosation of secondary amines, such as dimethylamine, diethylamine, proline, hydroxyproline, N-methylaminoacetonitrile, N-methylaminopropionitrile, and sarcosine. The nitrosating agent generated by the reaction between ascorbic acid and nitrite ion appears to be oxyhyponitrite ion (N2O3-2).