Helsby N A, Zhu S, Pearson A E, Tingle M D, Ferguson L R
Auckland Cancer Society Research Centre, Faculty of Medicine and Health Science, The University of Auckland, Private Bag 92019, 1000, Auckland, New Zealand.
Mutat Res. 2000 Nov 6;454(1-2):77-88. doi: 10.1016/s0027-5107(00)00101-9.
Diets containing wheat bran (WB) protect against cancers of the colon or breast 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), inclusion of 10% wheat bran in the diet led to an apparent reduction in IQ metabolites but not of intact IQ in plasma. In the present study, male Wistar rats were fed diets containing 0, 10 or 20% wheat bran, and effects on xenobiotic metabolising enzymes compared. Wheat bran-supplementation showed differential effects on phase I enzymes, significantly increasing the activity of hepatic cytochrome P450 isozyme CYP3A2, but slightly reducing the activity of CYP1A1/2. The activities of both hepatic phase II detoxification enzymes glutathione-S-transferase and glucuronosyl transferase were also reduced. Western blotting revealed similar effects on expression of the proteins. Interestingly, the expression of xenobiotic metabolising enzymes (XME) in the colon appeared to be modulated independently of hepatic XME. Although the wheat bran-supplemented diet still led to an increased expression of CYP3A, it now slightly increased CYP1A in the colon. However, 20% wheat bran significantly increased the expression of both glutathione transferase isozymes, GST A1 & A2, in the colon. Natures Gold (NG) is a commercial wheat bran derivative which is lower than wheat bran in dietary fibre, but enriched in vitamins, minerals and various phytochemicals. Dietary supplementation with 20% Natures Gold 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 metabolites was investigated using the Salmonella/mammalian microsome mutagenicity test. The activation of IQ and benzo[a]pyrene, but not cyclophosphamide, to a mutagen by hepatic S9 from wheat bran-fed or Natures Gold-fed rats was significantly reduced compared with S9 from animals on a diet lacking wheat bran. We suggest that modulation of xenobiotic metabolising enzymes may be an important component of cancer protection by wheat bran, and this effect may relate to micronutrients or cancer-protective non-nutrient phytochemicals rather more than to dietary fibre.
含麦麸（WB）的饮食可预防大鼠的结肠癌或乳腺癌，对人类可能也有益处。在之前一项用致癌物2-氨基-3-甲基咪唑[4,5-f]喹啉（IQ）处理大鼠的研究中，饮食中添加10%的麦麸可使血浆中IQ代谢物明显减少，但完整的IQ无明显变化。在本研究中，给雄性Wistar大鼠喂食含0%、10%或20%麦麸的饮食，并比较其对外源生物代谢酶的影响。补充麦麸对I相酶有不同影响，显著增加肝脏细胞色素P450同工酶CYP3A2的活性，但略微降低CYP1A1/2的活性。肝脏II相解毒酶谷胱甘肽-S-转移酶和葡萄糖醛酸转移酶的活性也降低。蛋白质免疫印迹显示对蛋白质表达有类似影响。有趣的是，结肠中外源生物代谢酶（XME）的表达似乎独立于肝脏XME进行调节。虽然补充麦麸的饮食仍导致CYP3A表达增加，但现在结肠中CYP1A略有增加。然而，20%的麦麸显著增加了结肠中谷胱甘肽转移酶同工酶GST A1和A2的表达。天然金（NG）是一种商业麦麸衍生物，其膳食纤维含量低于麦麸，但富含维生素、矿物质和各种植物化学物质。补充20%的天然金饮食导致的趋势与喂食麦麸的大鼠相似，但对肝脏和结肠酶的影响更显著。使用沙门氏菌/哺乳动物微粒体诱变性试验研究了这些变化对致癌物活化为诱变代谢物的意义。与喂食不含麦麸饮食的动物的S9相比，喂食麦麸或天然金的大鼠肝脏S9将IQ和苯并[a]芘而非环磷酰胺活化为诱变剂的能力显著降低。我们认为，外源生物代谢酶的调节可能是麦麸预防癌症的一个重要组成部分，这种作用可能更多地与微量营养素或具有癌症预防作用的非营养植物化学物质有关，而非膳食纤维。
