This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rao, M. S. Articles by Reddy, J. K. Search for Related Content PubMed PubMed Citation Articles by Rao, M. S. Articles by Reddy, J. K.

Hepatocarcinogenicity of Dehydroepiandrosterone in the Rat¹

Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611-3008

Dehydroepiandrosterone, a major secretory steroid bormone of the human adrenal gland, possesses mitoinhibitory and anticarcinogenic properties. It also induces peroxisome proliferation in the livers of rats and mice. Because peroxisome proliferators exhibit hepatocarcinogenic potential, it is necessary to examine the long term hepatic effects of dehydroepiandrosterone since this hormone is contemplated for use as a potential cancer chemopreventive agent in humans. Dehydroeplandrosterone was administered in the diet at a concentration of 0.45% to F-344 rats for up to 84 weeks. At the termination of the experiment, 14 of 16 rats developed hepatocellular carcinomas. Liver tumors induced by dehydroepiandrosterone lacked -glutamyl transpeptidase and glutathione S-transferase (placental form); these phenotypic properties are identical to the features exhibited by liver tumors induced by other peroxisome proliferators. Dehydroepiandrosterone was also shown to markedly inhibit liver cell [³H]thymidine labeling indices, suggesting that cell proliferation is not a critical feature in liver tumor development with this agent. These results show that although dehydroepiandrosterone exerts anticarcinogenic effects in a variety of tissues, the peroxisome-proliferative property makes it a hepatocarcinogen.

¹ This work was supported by NIH Grant GM23750 and a Veterans Affairs Merit Review Program.

² To whom requests for reprints should be addressed.

Received 2/14/92. Accepted 3/31/92.

This article has been cited by other articles:

				V. Tamasi, K. K. M. Miller, S. L. Ripp, E. Vila, T. E. Geoghagen, and R. A. Prough Modulation of Receptor Phosphorylation Contributes to Activation of Peroxisome Proliferator Activated Receptor {alpha} by Dehydroepiandrosterone and Other Peroxisome Proliferators Mol. Pharmacol., March 1, 2008; 73(3): 968 - 976. [Abstract] [Full Text] [PDF]

				K. Kohalmy, V. Tamasi, L. Kobori, E. Sarvary, J.-M. Pascussi, P. Porrogi, D. Rozman, R. A. Prough, U. A. Meyer, and K. Monostory Dehydroepiandrosterone Induces Human CYP2B6 through the Constitutive Androstane Receptor Drug Metab. Dispos., September 1, 2007; 35(9): 1495 - 1501. [Abstract] [Full Text] [PDF]

				D. L. McCormick, W. D. Johnson, N. M. Kozub, K.V.N. Rao, R. A. Lubet, V. E. Steele, and M. C. Bosland Chemoprevention of rat prostate carcinogenesis by dietary 16{alpha}-fluoro-5-androsten-17-one (fluasterone), a minimally androgenic analog of dehydroepiandrosterone Carcinogenesis, February 1, 2007; 28(2): 398 - 403. [Abstract] [Full Text] [PDF]

				C Suarez, J Vela, I Garcia-Tornadu, and D Becu-Villalobos Dehydroepiandrosterone (DHEA) modulates GHRH, somatostatin and angiotensin II action at the pituitary level J. Endocrinol., April 1, 2005; 185(1): 165 - 172. [Abstract] [Full Text] [PDF]

				K. K. M. Miller, J. Cai, S. L. Ripp, W. M. Pierce Jr., T. H. Rushmore, and R. A. Prough STEREO- AND REGIOSELECTIVITY ACCOUNT FOR THE DIVERSITY OF DEHYDROEPIANDROSTERONE (DHEA) METABOLITES PRODUCED BY LIVER MICROSOMAL CYTOCHROMES P450 Drug Metab. Dispos., March 1, 2004; 32(3): 305 - 313. [Abstract] [Full Text] [PDF]

				D. Mayer, K. Forstner, and K. Kopplow Induction and Modulation of Hepatic Preneoplasia and Neoplasia in the Rat by Dehydroepiandrosterone Toxicol Pathol, January 1, 2003; 31(1): 103 - 112. [Abstract] [PDF]

				H. P. Ciolino, C. J. MacDonald, and G. C. Yeh Inhibition of Carcinogen-activating Enzymes by 16{alpha}-Fluoro-5-androsten-17-one Cancer Res., July 1, 2002; 62(13): 3685 - 3690. [Abstract] [Full Text] [PDF]

				M. M. Simile, M. R. De Miglio, D. Calvisi, M. R. Muroni, M. Frau, G. Asara, L. Daino, L. Deiana, R. M. Pascale, and F. Feo Long-term dehydroepiandrosterone and 16{{alpha}}-fluoro-5-androsten-17-one administration enhances DNA synthesis and induces expression of c-fos and c-Ha-ras in a selected population of preneoplastic lesions in liver of diethylnitrosamine-initiated rats Carcinogenesis, February 1, 2001; 22(2): 301 - 308. [Abstract] [Full Text] [PDF]

				K. V. N. Rao, W. D. Johnson, M. C. Bosland, R. A. Lubet, V. E. Steele, G. J. Kelloff, and D. L. McCormick Chemoprevention of Rat Prostate Carcinogenesis by Early and Delayed Administration of Dehydroepiandrosterone Cancer Res., July 1, 1999; 59(13): 3084 - 3089. [Abstract] [Full Text] [PDF]

				T. D. Pugh, T. D. Oberley, and R. Weindruch Dietary Intervention at Middle Age: Caloric Restriction but not Dehydroepiandrosterone Sulfate Increases Lifespan and Lifetime Cancer Incidence in Mice Cancer Res., April 1, 1999; 59(7): 1642 - 1648. [Abstract] [Full Text] [PDF]

				C. L. Rokos and B. J. Ledwith Peroxisome Proliferators Activate Extracellular Signal-regulated Kinases in Immortalized Mouse Liver Cells J. Biol. Chem., May 16, 1997; 272(20): 13452 - 13457. [Abstract] [Full Text] [PDF]

				B. J. Ledwith, C. J. Pauley, L. K. Wagner, C. L. Rokos, D. W. Alberts, and S. Manam Induction of Cyclooxygenase-2 Expression by Peroxisome Proliferators and Non-tetradecanoylphorbol 12,13-Myristate-type Tumor Promoters in Immortalized Mouse Liver Cells J. Biol. Chem., February 7, 1997; 272(6): 3707 - 3714. [Abstract] [Full Text] [PDF]

				Androgen Replacement: An Idea Whose Time Hasn't Come Journal Watch Women's Health, September 1, 1996; 1996(901): 22 - 22. [Full Text]