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Carcinogen-induced Lesions in the Rat Pancreas: Effects of Varying Levels of Essential Fatty Acid¹

Departments of Pharmacology and Toxicology [B. D. R., K. J. B., C. D. T.] and Pathology [D. S. L.], Dartmouth Medical School, Hanover, New Hampshire 03756

The ingestion of high levels of fats, especially unsaturated fats, has been shown to enhance carcinogenesis in a variety of experimental model systems. Recently attention has focused upon the unsaturated linoleic fatty acid (18:26) as a key component for this postinitiation enhancement. We have investigated the dose-effect relationship of this essential fatty acid (EFA), in a well-characterized experimental model of pancreatic cancer. Male Lewis rats were given injections i.p. of azaserine (30 mg/kg) at 14 days of age. The pups were weaned to test diets that contained 20% total dietary fat with EFA compositions varying from 0.5 to 11.5% of the diet. After 4 months of feeding these 20% fat diets, the pancreases were evaluated in situ for grossly visible tumors and microscopically for the number and size of the azaserine-induced, putative preneoplastic lesions (foci). Grossly visible tumors increased significantly in number as the EFA content of the diet increased. Two populations of microscopic foci were observed in these azaserine-initiated rats; namely, acidophilic foci and basophilic foci. Quantitative stereological analyses of these foci revealed that the acidophilic population of foci increased in both number and size as the EFA content of the diet increased. This increase was particularly apparent from 4.4 to 8.5% dietary EFA content. The basophilic population showed no similar response to increasing dietary EFA. These results indicate that the minimum dietary EFA required for enhancement of azaserine-induced, pancreatic carcinogenesis by a high fat diet lies in the range of 4 to 8%.

¹ This work was supported by a grant from Best Foods/CPC International, Englewood Cliffs, NJ 07632.

² To whom requests for reprints should be addressed.

Received 8/21/84. Revised 7/11/85. Accepted 7/26/85.

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