ILAR Sign up for PNAS Online eTocs
Link: Info for AuthorsLink: Editorial BoardLink: AboutLink: SubscribeLink: AdvertiseLink: ContactLink: Sitemap Link: PNAS Home
Proceedings of the National Academy of Sciences
Link: Current Issue "" Link: Archives "" Link: Online Submission ""  Link: Advanced Search

Published online on March 24, 2003, 10.1073/pnas.0437929100
PNAS | April 1, 2003 | vol. 100 | no. 7 | 3913-3918


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supporting Figures
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via ISI Web of Science (24)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bhat, H. K.
Right arrow Articles by Vadgama, J. V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bhat, H. K.
Right arrow Articles by Vadgama, J. V.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg  
What's this?

 Previous Article  | Table of Contents |  Next Article 

Biochemistry
 Critical role of oxidative stress in estrogen-induced carcinogenesis

(tumor|hormonal carcinogenesis|menadione|prostaglandin|metabolic activation)

Hari K. Bhat*,dagger , Gloria CalafDagger , Tom K. Hei*,Dagger , Theresa Loya§, and Jaydutt V. Vadgama

* Department of Environmental Health Sciences, Mailman School of Public Health, 60 Haven Avenue-B1, Columbia University, New York, NY 10032; Dagger  Center for Radiological Research, Columbia University, New York, NY 10032; and Departments of § Pathology and  Medicine, Charles Drew University, Los Angeles, CA 90059

Communicated by Donald C. Malins, Pacific Northwest Research Institute, Seattle, WA, December 27, 2002 (received for review August 22, 2002)

Mechanisms of estrogen-induced tumorigenesis in the target organ are not well understood. It has been suggested that oxidative stress resulting from metabolic activation of carcinogenic estrogens plays a critical role in estrogen-induced carcinogenesis. We tested this hypothesis by using an estrogen-induced hamster renal tumor model, a well established animal model of hormonal carcinogenesis. Hamsters were implanted with 17beta -estradiol (beta E2), 17alpha -estradiol (alpha E2), 17alpha -ethinylestradiol (alpha EE), menadione, a combination of alpha E2 and alpha EE, or a combination of alpha EE and menadione for 7 months. The group treated with beta E2 developed target organ specific kidney tumors. The kidneys of hamsters treated with alpha E2, alpha EE, or menadione alone did not show any gross evidence of tumor. Kidneys of hamsters treated with a combination of alpha E2 and alpha EE showed early signs of proliferation in the interstitial cells. Kidneys of hamsters treated with a combination of menadione and alpha EE showed foci of tumor with congested tubules and atrophic glomeruli. beta E2-treated tumor-bearing kidneys showed >2-fold increase in 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha ) levels compared with untreated controls. Kidneys of hamsters treated with a combination of menadione and alpha EE showed increased 8-iso-PGF2alpha levels compared with untreated controls, whereas no increase in 8-iso-PGF2alpha was detected in kidneys of alpha EE-treated group. A chemical known to produce oxidative stress or a potent estrogen with poor ability to produce oxidative stress, were nontumorigenic in hamsters, when given as single agents, but induced renal tumors, when given together. Thus, these data provide evidence that oxidant stress plays a crucial role in estrogen-induced carcinogenesis.

dagger To whom correspondence should be addressed. E-mail: hb2009{at}columbia.edu.

www.pnas.org/cgi/doi/10.1073/pnas.0437929100
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg    What's this?


This article has been cited by other articles in HighWire Press-hosted journals:


Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
S. K. Quick, P. G. Shields, J. Nie, M. E. Platek, S. E. McCann, A. D. Hutson, M. Trevisan, D. Vito, R. Modali, T. A. Lehman, et al.
Effect Modification by Catalase Genotype Suggests a Role for Oxidative Stress in the Association of Hormone Replacement Therapy with Postmenopausal Breast Cancer Risk
Cancer Epidemiol. Biomarkers Prev., May 1, 2008; 17(5): 1082 - 1087.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
N. N.C. Tam, I. Leav, and S.-M. Ho
Sex Hormones Induce Direct Epithelial and Inflammation-Mediated Oxidative/Nitrosative Stress That Favors Prostatic Carcinogenesis in the Noble Rat
Am. J. Pathol., October 1, 2007; 171(4): 1334 - 1341.
[Abstract] [Full Text] [PDF]

Home page
 Ann. N. Y. Acad. Sci.Home page
J. E TROSKO
From Adult Stem Cells to Cancer Stem Cells: Oct-4 Gene, Cell-Cell Communication, and Hormones during Tumor Promotion
Ann. N.Y. Acad. Sci., November 1, 2006; 1089(1): 36 - 58.
[Abstract] [Full Text] [PDF]

Home page
 Ann. N. Y. Acad. Sci.Home page
K. PROKAI-TATRAI and L. PROKAI
Impact of Metabolism on the Safety of Estrogen Therapy
Ann. N.Y. Acad. Sci., June 1, 2005; 1052(1): 243 - 257.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
J.-Y. Guo, X. Li, J. D. Browning Jr., G. E. Rottinghaus, D. B. Lubahn, A. Constantinou, M. Bennink, and R. S. MacDonald
Dietary Soy Isoflavones and Estrone Protect Ovariectomized ER{alpha}KO and Wild-Type Mice from Carcinogen-Induced Colon Cancer
J. Nutr., January 1, 2004; 134(1): 179 - 182.
[Abstract] [Full Text] [PDF]