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Effects of Dietary Fats and Soybean Protein on Azaserine-induced Pancreatic Carcinogenesis and Plasma Cholecystokinin in the Rat¹

Department of Pharmacology and Toxicology [B. D. R., P. V. K.] and Department of Physiology [B. R. E.], Dartmouth Medical School, Hanover, New Hampshire 03756; and Department of Medicine, Nassau County Medical Center, East Meadow, New York 11554 [M. P.]

Both dietary unsaturated fat and raw soybean products are known to enhance pancreatic carcinogenesis when fed during the postinitiation phase. A comparison of these two dietary components was made to evaluate the relative potency of each ingredient for enhancing pancreatic carcinogenesis and to determine if this enhancement was correlated with an increase in plasma cholecystokinin (CCK) levels. Male Wistar rats were initiated with a single dose of azaserine (30 mg/kg body weight) at 14 days of age. The rats were weaned to test diets formulated from purified ingredients. Dietary protein at 20% by weight was either casein or soy protein isolate (heat treated or raw). Corn oil was the unsaturated fat of major interest and it was fed at either 5 or 20% by weight. Pancreases were quantitatively evaluated for carcinogen-induced lesions at 2- and 4-month postinitiation. In a second experiment designed to closely mimic the above experiment, rats were implanted with cannulae which allowed plasma to be repetitively sampled over a 2.5-week period during which the test diets were fed. Plasma was collected both prior to introduction of the test diets and afterwards. Plasma CCK was measured by a specific radioimmunoassay. Both the 20% corn oil diet and the raw soy protein isolate diet enhanced pancreatic carcinogenesis. The effects of the raw soy protein isolate on the growth of the carcinogen-induced lesions were significantly greater than the effects of the 20% corn oil diet. Plasma CCK values were not elevated in the rats fed the 20% corn oil diet, but they were significantly elevated in the rats fed the raw soy protein isolate. Heat-treated soy protein isolate neither enhanced carcinogenesis nor elevated the plasma CCK level. This study demonstrates that certain plant proteins enhance the growth of carcinogen-induced pancreatic foci and that this effect is considerably greater than the enhancement by high levels of dietary unsaturated fat. Furthermore, the enhancement by the raw soy protein isolate may be mediated by CCK; but this does not appear to be the mechanism by which the unsaturated fat, corn oil, enhances pancreatic carcinogenesis.

¹ This work was supported in part by USPHS Grants CA-26594, from the National Cancer Institute, and ES-07104, from the National Institute of Environmental Health Sciences, and the Meadowbrook Medical Education and Research Foundation.

² To whom requests for reprints should be addressed.

³ Present address: Nova Pharmaceutical Corporation, 5210 Eastern Avenue, Baltimore, MD 21224–2788.

Received 12/26/85. Revised 6/25/86. Revised 9/29/86. Accepted 11/21/86.

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