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 Abou-El-Ela, S. H. Articles by Bunce, O. R. Search for Related Content PubMed PubMed Citation Articles by Abou-El-Ela, S. H. Articles by Bunce, O. R.

Effects of D,L-2-Difluoromethylornithine and Indomethacin on Mammary Tumor Promotion in Rats Fed High n-3 and/or n-6 Fat Diets¹

Department of Pharmacology and Toxicology, College of Pharmacy [S. H. A., A. E. W., O. R. B.] and Department of Pathology, College of Veterinary Medicine [K. W. P., R. L. F.], University of Georgia, Athens, GA 30602; and Department of Preventive Medicine and Community Health [R. C.], University of Texas Medical Branch, Galveston, Texas 77550-2779

Virgin female Sprague-Dawley rats (50 days of age) were administered a single intragastric 10-mg dose of 7,12-dimethylbenz(a)anthracene (DMBA). Twenty-one days later they were placed on diets containing either 20% corn oil (CO), 15% menhaden oil plus 5% corn oil (MO + CO0, 20% CO plus 0.5% w/w of the irreversible ornithine decarboxylase inhibitor, D,L-2-difluoromethylornithine (CO + DFMO), 20% CO plus 0.004% w/w of the cyclooxygenase inhibitor indomethacin (CO + INDO), 20% CO + 0.004% INDO + 0.5% DFMO (CO + INDO + DFMO), or 15% MO + 5% CO + 0.5% DFMO (MO + CO + DFMO). The incidence of DMBA-induced mammary tumors was significantly reduced in rats fed diets containing DFMO but not in rats fed the diet containing indomethacin. Incidences of mammary tumors at 16 weeks post-DMBA were 86% in rats fed the CO diet, 83% in rats ingesting the diet containing CO + INDO, 28% in rats fed CO + DFMO, 32% in rats fed diet containing CO + INDO + DFMO, 59% in rats fed the MO + CO diet, and 24% in rats fed the MO + CO + DFMO diet. The average number of tumors and tumor burden per tumor-bearing rat were reduced and tumor latency was increased in all rats fed diets containing DFMO. Body weight gain, but not food intake, of rats fed the 20% fat + 0.5% DFMO diets was significantly less than in rats fed the 20% fat diets. Prostaglandin E and leukotriene (LTB₄) syntheses, ODC activity and mammary tumorigenesis were significantly inhibited by feeding the diet containing menhaden oil or by adding 0.5% DFMO to any of the high fat diets. Feeding a 20% CO diet containing 0.004% INDO significantly reduced prostaglandin synthesis and ODC activity and increased LTB₄ synthesis of mammary tumors but did not inhibit mammary tumorigenesis. This study suggests that the 5-lipoxygenase product LTB₄ may be involved in mammary tumor production. Whereas a decrease in LTB₄ appears to be associated with a decrease in tumorigenesis, an increase (as seen in the indomethacin group) was not associated with any change in the tumorigenic response.

¹ Supported in part by grants received from Amideast and the Egyptian Cultural and Education Bureau.

² To whom requests for reprints should be addressed, at Department of Pharmacology and Toxicology, College of Pharmacy, University of Georgia, Athens, GA 30602.

Received 6/21/88. Revised 10/12/88. Revised 12/13/88. Accepted 12/20/88.

This article has been cited by other articles:

				P. D. Terry, J. B. Terry, and T. E. Rohan Long-Chain (n-3) Fatty Acid Intake and Risk of Cancers of the Breast and the Prostate: Recent Epidemiological Studies, Biological Mechanisms, and Directions for Future Research J. Nutr., December 1, 2004; 134(12): 3412S - 3420S. [Abstract] [Full Text] [PDF]

				W. E. Hardman (n-3) Fatty Acids and Cancer Therapy J. Nutr., December 1, 2004; 134(12): 3427S - 3430S. [Abstract] [Full Text] [PDF]

				P. D Terry, T. E Rohan, and A. Wolk Intakes of fish and marine fatty acids and the risks of cancers of the breast and prostate and of other hormone-related cancers: a review of the epidemiologic evidence Am. J. Clinical Nutrition, March 1, 2003; 77(3): 532 - 543. [Abstract] [Full Text] [PDF]

				W. E. Hardman Omega-3 Fatty Acids to Augment Cancer Therapy J. Nutr., November 1, 2002; 132(11): 3508S - 3512. [Abstract] [Full Text] [PDF]

				E. Half, X. M. Tang, K. Gwyn, A. Sahin, K. Wathen, and F. A. Sinicrope Cyclooxygenase-2 Expression in Human Breast Cancers and Adjacent Ductal Carcinoma in Situ Cancer Res., March 1, 2002; 62(6): 1676 - 1681. [Abstract] [Full Text] [PDF]

				V. E. Steele, C. A. Holmes, E. T. Hawk, L. Kopelovich, R. A. Lubet, J. A. Crowell, C. C. Sigman, and G. J. Kelloff Lipoxygenase Inhibitors as Potential Cancer Chemopreventives Cancer Epidemiol. Biomarkers Prev., May 1, 1999; 8(5): 467 - 483. [Abstract] [Full Text]