Antimutagenic effects of wheat bran diet through modification of xenobiotic metabolising enzymes

Diets containing wheat bran (WB) protect against cancers of the colon or br east in rats, and may be beneficial in humans. In a previous study of rats treated with the carcinogen 2-amino-3-methylimidazo[4,5;f]quinoline (IQ), i nclusion of 10% wheat bran in the diet led to an apparent reduction in IQ m etabolites but not of intact IQ in plasma. In the present study, male Wista r rats were fed diets containing 0, 10 or 20% wheat bran, and effects on xe nobiotic metabolising enzymes compared. Wheat bran-supplementation showed d ifferential effects on phase I enzymes, significantly increasing the activi ty of hepatic cytochrome P450 isozyme CYP3A2, but slightly reducing the act ivity of CYP1A1/2. The activities of both hepatic phase II detoxification e nzymes glutarhione-S-transferase and glucuronosyl transferase were also red uced. Western blotting revealed similar effects on expression of the protei ns. Interestingly, the expression of xenobiotic metabolising enzymes (XME) in the colon appeared to be modulated independently of hepatic XME. Althoug h the wheat bran-supplemented diet still led to an increased expression of CYP3A, it now slightly increased CYP1A in the colon. However, 20% wheat bra n significantly increased the expression of both glutathione transferase is ozymes, GST A1 & A2, in the colon. Natures Gold(TM) (NG) is a commercial wh eat bran derivative which is lower than wheat bran in dietary fibre, but en riched in vitamins, minerals and various phytochemicals. Dietary supplement ation with 20% Natures Gold(TM) led to similar trends as seen in wheat bran -fed rats, but more potent effects in both hepatic and colonic enzymes. The significance of these changes for activation of carcinogens to mutagenic m etabolites was investigated using the Salmonella/mammalian microsome mutage nicity test. The activation of IQ and benzo[a]pyrene, but not cyclophospham ide, to a mutagen by hepatic S9 from wheat bran-fed or Natures Gold(TM)-fed rats was significantly reduced compared with S9 from animals on a diet lac king wheat bran. We suggest that modulation of xenobiotic metabolising enzy mes may be an important component of cancer protection by wheat bran, and t his effect may relate to micronutrients or cancer-protective non-nutrient p hytochemicals rather more than to dietary fibre, (C) 2000 Elsevier Science B.V. All rights reserved.