Effect of varying levels of dietary protein on tumor development and lipid metabolism in rats exposed to aflatoxin

Abstract

Reports in the literature concerning the relationship of protein nutrition to aflatoxicosis are contradictory. In an attempt to elucidate this relationship more clearly, we have examined the effects of low, normal, and high protein-containing diets on tumor incidence and development, as well as on several biochemical indices, in rats which have been exposed to low levels of aflatoxin in a “chronic” rather than “acute” situation. In our study, male weanling rats were place for 3 months on otherwise adequate diets containing either 8, 22, or 30% casein with and without aflatoxin B₁ at 1.7 ppm. Half of the animals in each group received diets which were further supplemented with the amino acid, cystine, at 0.6% of the diet. (Sulfur-containing amino acids are the most limiting amino acids in casein, and the addition of cystine to the diet serves to improve the biological quality of the protein source.) After 3 months the animals were fed control diets without aflatoxin until they were killed at 1 year. Weight gain was markedly decreased and liver weights increased in response to aflatoxin in all groups except those on the low protein diets, where aflatoxin had no effect on these protein diets, where aflatoxin had no effect on these indices. No tumors were found in the livers of rats fed the low protein, aflatoxin-supplemented diet. In the other groups, the severity of the liver involvement increased progressively with increased protein levels in the diet. When cystine was included in the diet, tumors were observed also in the animals fed the low protein diet; furthermore, the livers of those animals on “normal” and high protein diets were much more severely involved than were the livers of animals on non-cystine supplemented diets. Plasma cholesterol levels were increased in response to aflatoxin when the diets containing 22 and 30% protein were fed and when cystine was included in the 8% protein diet. Liver cholesterol levels were increased in response to aflatoxin in all groups except in those receiving the low protein diets. Among these latter animals, aflatoxin administration had no effect on liver cholesterol values. Changes as a result of aflatoxin administration were also observed in the fatty acid composition of sterol esters, triglycerides, and phospholipids of liver and tumor tissue.