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Toxicologic Pathology
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Journal Article

Inhibition of Tumor Development by Dehydroepiandrosterone and Related Steroids

Arthur G. Schwartz

Fels Research Institute and Department of Microbiology, Temple University Medical School, Philadelphia, Pennsylvania 19140

Laura Pashko

Fels Research Institute and Department of Microbiology, Temple University Medical School, Philadelphia, Pennsylvania 19140

Jeannette M. Whitcomb

Fels Research Institute and Department of Microbiology, Temple University Medical School, Philadelphia, Pennsylvania 19140

The naturally occurring adrenal steroid, dehydroepiandrosterone (DHEA), is a potent non-competitive inhibitor of mammalian glucose-6-phosphate dehydrogenase (G6PDH). Oral administration of DHEA to mice inhibits spontaneous breast cancer and chemically induced tumors of the lung and colon. Topical application of DHEA to mouse skin inhibits 7,12-dimethylbenz(a)anthracene (DMBA)-initiated and tetra-decanoylphorbol-13-acetate (TPA)-promoted papillomas and DMBA-induced carcinomas at both the initiation and promotion phase. Evidence is presented that critical steps in the initiation process (mixed-function oxidase activation of a carcinogen) and promotion process (enhanced rates of cell proliferation and superoxide formation) all require NADPH and may be inhibited by DHEA and structural analogs as a result of a lowering of the NADPH cellular pool. Results obtained by others with fibroblasts and lymphocytes from individuals with the Mediterranean variant of G6PDH deficiency also indicate that a reduction in the NADPH cellular pool confers resistance to benzo(a)pyrene. Preliminary data suggest that food restriction may depress G6PDH levels and this may contribute to the tumor preventive effect of underfeeding.

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Toxicologic Pathology, Vol. 14, No. 3, 357-362 (1986)
DOI: 10.1177/019262338601400312
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This Article
Right arrow Abstract Freely available
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