Dietary Enhancement of Nitrosamine Carcinogenesis1

Previous studies have shown that a diet high in fat and marginally deficient in lipotropes enhances aflatoxin B] hepatocarcinogenesis and depresses hepatic drug metabolism in rats. In this study we have compared induction of tumors by jV-nitrosodimethylamine, ./V-nitrosodiethylamine, or jV-nitrosodibutylamine in normal or marginally lipotrope-deficient rats fed a high-fat diet. The deficiency significantly enhanced hepatocarcinogenesis by both JV-nitrosodiethylamine and Nnitrosodibutylamine and may have enhanced esophageal carcinogenesis by ./V-nitrosodiethylamine. Induction of tumors by yV-nitrosodimethylamine and jV-nitrosodimethylamine metabolism in vitro in liver slices were not significantly affected by the diet. protein. Before the effects of individual diets were examined, studies were undertaken to compare the effect of the 2 diets on carcinogenesis by other compounds and in other organs in order to determine whether enhancement of carcinogenesis by the deficient diet was specific for AFB!. The 1st group of carcinogens studied was the nitrosamines, which comprise a large group of tumor-inducing compounds in many different organs of expermental animals. They are also found in human foods and are suspected to be a causative factor in human esophageal carcinoma (1, 3,6,8, 10, 24). The carcinogenic effect of the simplest compound, DMN, is susceptible to dietary alteration. Protein deficiency increases the number of renal tumors induced, while depressing induction of hepatic tumors, and decreases the ability of the liver to metabolize DMN (7, 13, 27).