Influence of Dehydroepiandrosterone on G-6-PD Activity and 3H-Thymidine Uptake of Human Lymphocytes In Vitro

Abstract

Dehydroepiandrosterone (DHEA) was found to inhibit experimental cancer development in mouse and rat lung, colon and mammary gland. Since DHEA is a potent inhibitor of mammalian G-6-PD, the hypothesis that the compound could inhibit cell proliferation through an inhibition of the pentose phosphate pathway has been formulated. We studied the effects of DHEA on the proliferation in vitro of human lymphocytes induced by several mitogens (PHA, ConA and PWM), measuring 3H-thymidine uptake. DHEA inhibited 3H-thymidine uptake of mitogen-stimulated cells from both G-6-PD⁺ and G-6-PD^- (mediterranean type deficiency) individuals in a dose-dependent and reversible fashion. The inhibitory effect was found even if DHEA was added to cells in the last hours of culture, simultaneously with the addition of 3H-thymidine. These data suggest that the inhibition of thymidine uptake induced by DHEA on human lymphocytes probably does not depend on the inhibition of G-6-PD.

References

1. Baulieu EE , and Bigbee JW (1963). Conversion of 3H dehydroepiandrosterone (3alpha-hydroxy-delta5-androsten-17-one) sulfate to 3H-estrogens in normal pregnant women. J. Clin. Endocrinol. Metab. 23: 1298–1301.

2. Beutler E , Bigbee JW , Bigbee JW , Bigbee JW , Bigbee JW , and Bigbee JW (1977). International committee for standardization in haematology: Recommended methods for red cell enzyme analysis. Brit. J. Haematol. 35: 331–340.

3. Glock GE , and Bigbee JW (1953). Further studies on the properties and assay of glucose-6-phosphate and 6-phospho-gluconate dehydrogenase of rat liver. Biochem. J. 55: 400–408.

4. Henderson E , Schwartz A , Pashko L , Abou-Gharbia M , and Bigbee JW (1981). Dehydroepiandrosterone and 16-alpha-bromo-epiandrosterone: Inhibitors of Epstein Barr virus induced transformation of human lymphocytes. Carcinogenesis 2: 683–686.

5. Manconi PE , Bigbee JW , Bigbee JW , Bigbee JW , and Bigbee JW (1983). Alpha-naphthyl acetate esterase activity in human lymphocytes. Distribution in lymphocyte subpopulations and in mitogen-activated cells. Scand. J. Immunol. 9: 99–104.

6. Marks PA , and Bigbee JW (1960). Inhibition of mammalian glucose 6-phosphate dehydrogenase by steroids. Proc. Natl. Acad. Sci. (USA) 46: 447–452.

7. Nyce JW , Bigbee JW , Bigbee JW , and Bigbee JW (1984). Inhibition of 1,2-dimethylhydrazine induced colon tumorigenesis in Balb/c mice by dehydroepiandrosterone. Carcinogenesis 5: 57–62.

8. Schwartz AG (1979). Inhibition of spontaneous breast cancer formation in female C3H-Avy/A mice by long term treatment with dehydroepiandrosterone. Cancer Res. 39: 1129–1132.

9. Schwartz AG , Hard G , Pashko L , Abou-Ghardia M , and Bigbee JW (1981). Dehydroepiandrosterone: An anti-obesity and anti-carcinogenesis agent. Nutr. Cancer 3: 46–53.

10.

10. Schwartz AG , Bigbee JW , and Bigbee JW (1983). Dehydroepiandrosterone: An anti-cancer and possible anti-aging substance. In: Intervention in the aging process, Part A: Quantitation, epidemiology and clinical research. Alan R. Liss, Inc., New York, N.Y., pp. 267–278.

11.

11. Schwartz AG , and Bigbee JW (1981). Inhibition of 1,12-dimethylbenz-(a)anthracene and urethane-induced lung tumor formation in A/J mice by long term treatment with dehydroepiandrosterone. Carcinogenesis 2: 1335–1337.