QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Purchase Article View Shopping Cart 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 Clinton, S. K. Articles by Visek, W. J. Search for Related Content PubMed PubMed Citation Articles by Clinton, S. K. Articles by Visek, W. J.

The Combined Effects of Dietary Fat and Estrogen on Survival, 7,12-Dimethylbenz(a)anthracene-Induced Breast Cancer and Prolactin Metabolism in Rats^1,2,

Steven K. Clinton^*,3, P. Shirley Li, Anthony L. Mulloy^**, Peter B. Imrey, Steven Nandkumar^# and Willard J. Visek

^* Divisions of Cancer Pharmacology and Clinical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115 Department of Physiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan 70101, Republic of China ^** Department of Medicine, Medical College of Georgia, Augusta, GA 30912 Departments of Medical Information Science, Community Health, and Statistics ^# Pathology Department Division of Nutritional Sciences, Department of Internal Medicine, College of Medicine, University of Illinois, Urbana, IL 61801

The relationships between dietary fact concentration (10 or 40% of energy), fat source (corn oil or beef tallow) and estrogen (control, ovariectomy or ovariectomy with estrogen replacement) to 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast carcinogenesis and survival in rats were studied in a 2 x 2 x 3 factorial experiment. Female Sprague-Dawley rats given DMBA (2.5 mg/100 g body wt, intragastric) at 55 d of age were randomly allocated to three groups 48 h later: sham ovariectomy (control), overiectomy (OVX) or ovariectomy with a subcutaneous estrogen implant (OVX₊E). Each group was subdivided into dietary groups fed 10 and 40% of energy as corn oil or beef tallow for 70 wk. OVX₊E rats exhibited serum estrogen concentrations in excess of physiologic values. Survival at 70 wk for the 3 hormonal groups was control 51%, OVX 67% and OVX₊E 13%. Mortality in controls was doubled by feeding a high fat diet; no diet effect was detected in OVX or OVX₊E rats. Palpable tumors developed in 74, 14 and 60% of control, OVX and OVX₊E rats, respectively. High fat diets approximately doubled the hazard of developing a palpable tumor. Adenocarcinoma prevalence was 58, 12 and 63% in control, OVX and OVX₊E rats, respectively. The odds of having any tumor, and adenocarcinoma of an adenoma were multiplied by 3.6, 2.8 and 2.3, respectively, for rats fed high vs. low fat. Additional studies showed that diet had no effect on serum prolactin or estrogen concentrations or metabolism and clearance of intravenously administered radiolabeled prolactin. We demonstrated that high dietary fat concentration enhances breast carcinogenesis independently of cyclic ovarian function, although the presence of estrogen may be a prerequisite for significant dietary modulation. The effect of fat on breast cancer is not mediated by major changes in systemic prolactin metabolism.

KEY WORDS: • rats • estrogen • prolactin • dietary fat • breast cancer

¹ Supported by the Public Health Service, National Institutes of Health, National Cancer Institute, Grant CA23326 and CA29629 to Dr. Visek and K07 CA01680 to Dr. Clinton.

² The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

³ To whom correspondence and reprint requests should be addressed.

Manuscript received 8 September 1993. Revision accepted 11 November 1994.

This article has been cited by other articles:

				C. D. Allred, K. F. Allred, Y. H. Ju, L. M. Clausen, D. R. Doerge, S. L. Schantz, D. L. Korol, M. A. Wallig, and W. G. Helferich Dietary genistein results in larger MNU-induced, estrogen-dependent mammary tumors following ovariectomy of Sprague-Dawley rats Carcinogenesis, February 1, 2004; 25(2): 211 - 218. [Abstract] [Full Text] [PDF]

				N. W. Istfan, Z.-Y. Chen, and S. Rex Fish oil slows S phase progression and may cause upstream shift of DHFR replication origin ori-beta in CHO cells Am J Physiol Cell Physiol, October 1, 2002; 283(4): C1009 - C1024. [Abstract] [Full Text] [PDF]