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Effect of the Prostaglandin Synthetase Inhibitor Indomethacin on 7,12-Dimethylbenz(a)anthracene-induced Mammary Tumorigenesis in Rats Fed Different Levels of Fat¹

Department of Experimental Therapeutics, Grace Cancer Drug Center, New York State Department of Health, Roswell Park Memorial Institute, Buffalo, New York 14263

The effect of the prostaglandin synthetase inhibitor indomethacin on the dietary fat enhancement of 7,12-dimethylbenz(a) anthracene-induced mammary tumorigenesis has been examined in female Sprague-Dawley rats. Rats were fed either a normal-fat or high-fat diet (5 or 18% corn oil, respectively) with or without 0.004% indomethacin, starting 3 days after a single intragastric intubation of 5 mg 7,12-dimethylbenz(a)anthracene. Results of this experiment demonstrated that indomethacin completely blocked the stimulatory effect of fat on tumorigenesis, as measured by a decreased tumor incidence, a decreased number of tumors per group, a decreased tumor size, and an increased latency. No effect of indomethacin was observed in rats fed the normal-fat diet. These data suggest that at least part of the stimulatory effect of polyunsaturated fat on 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis may be mediated through an increased synthesis of prostaglandins.

¹ This work was supported by Grants CA 13038 and CA 24538 from the National Cancer Institute.

² Parts of this work are from a thesis which was submitted to the faculty of the Roswell Park Division of the Graduate School of the State University of New York at Buffalo in partial fulfillment of the requirements for the degree of Master of Science.

³ To whom requests for reprints should be addressed, at Department of Experimental Therapeutics, Roswell Park Memorial Institute, 666 Elm St., Buffalo, N. Y. 14263.

Received 9/ 8/82. Accepted 4/29/83.

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