Journal Article

Chemoprevention of rat prostate carcinogenesis by dietary 16α-fluoro-5-androsten-17-one (fluasterone), a minimally androgenic analog of dehydroepiandrosterone

David L. McCormick, William D. Johnson, Nicole M. Kozub, K.V.N. Rao, Ronald A. Lubet, Vernon E. Steele and Maarten C. Bosland

in Carcinogenesis

Volume 28, issue 2, pages 398-403
Published in print September 2006 | ISSN: 0143-3334
Published online February 2007 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgl141
Chemoprevention of rat prostate carcinogenesis by dietary 16α-fluoro-5-androsten-17-one (fluasterone), a minimally androgenic analog of dehydroepiandrosterone

More Like This

Show all results sharing this subject:

  • Clinical Cytogenetics and Molecular Genetics

GO

Show Summary Details

Preview

Dehydroepiandrosterone (DHEA) is a potent inhibitor of prostate carcinogenesis in rats. However, concerns related to the possible androgenicity of DHEA may preclude its use for chemoprevention of human prostate cancer. Studies were performed to compare the androgenicity of DHEA and a fluorinated DHEA analog, 16α-fluoro-5-androsten-17-one (fluasterone), and to determine the chemopreventive activity of fluasterone in the rat prostate. Comparisons of accessory sex gland weight and histology in gonadectomized male rats demonstrated that fluasterone is less androgenic than is DHEA. Fluasterone conferred significant protection against prostate carcinogenesis induced in Wistar-Unilever rats by a sequential regimen of N-methyl-N-nitrosourea + testosterone. Chronic administration of fluasterone at levels of 2000 and 1000 mg/kg diet reduced the incidence of adenocarcinoma in the dorsolateral/anterior prostate from 64% in dietary controls to 28 and 31%, respectively. Other than a dose-related suppression of body weight gain, chronic exposure to fluasterone induced no clinical evidence of toxicity; suppression of body weight gain may be either a pharmacological effect or a minimally toxic effect of the compound. These data demonstrate that a minimally androgenic analog of DHEA protects against prostate carcinogenesis induced in rats by a chemical carcinogen + androgen. The reduced androgenicity of fluasterone may obviate toxicities associated with the androgenicity of the parent compound. On this basis, fluasterone merits consideration for evaluation in clinical trials for prostate cancer prevention. The chemopreventive activity of a non-androgenic DHEA analog suggests that at least a portion of the chemopreventive activity of DHEA in the rat prostate is unrelated to hormonal effects.

Journal Article.  4848 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.