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 (18:2 omega 6) 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%.