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Effects of Dietary Constituents on the Metabolism of Chemical Carcinogens¹

Department of Laboratory Medicine, and Pathology, University of Minnesota School of Medicine, Minneapolism Minnesota 55455

Dietary constituents of 2 types have been shown to affect the metabolism of chemical carcinogens by the microsomal mixed-function oxidase system. Naturally occurring inducers of increased activity of this system are present in plants. Cruciferous vegetables including Brussels sprouts, cabbage, and cauliflower are relatively potent in this regard, From these vegetables, three indoles with inducing activity have been identified. These are indole-3-acetonitrile, indole-3-carbinol, and 3,3'-diindolylmethane. A 2nd type of dietary constituent affecting the microsomal mixed-function oxidase system is added phenolic antioxidant, i.e., butylated hydroxyanisole (BHA) and butylated hydroxytoluene. Studies of the effect of BHA on metabolism of benzo(a)pyrene by liver microsomes have been carried out, BHA feeding results in microsomal changes. The cytochrome P-450 shows altered spectral characteristics, and the aryl hydrocarbon hydroxylase system of these microsomes has an increased sensitivity to inhibition by -naphthoflavone. In addition, there is a decrease in binding of metabolites of benzo(a)pyrene to DNA upon incubaton of these microsomes with benzo(a)pyrene. A number of experimental studies of induction of increased mixed function oxidase activity have shown that increased levels of activity protect against administration of chemical carcinogens. BHA and butylated hydroxytoluene also have been found to exert a protective effect against chemical carcinogens. Thus the constituents of the diet could be of consequence in the neoplastic response to exposure to carcinogens in the environment.

¹ Presented at the Conference on Nutrition in the Causation of Cancer, May 19 to 22, 1975, Key Biscayne, Fla. Supported by USPHS Grants CA-09599 and CA-14146 and Contract NO1-CP-33364 from the National Cancer Institute, NIH.