Pierre Fabrice, Freeman Amanda, Taché Sylviane, Van der Meer Roelof, Corpet Denis E
Ecole Nationale Vétérinaire Toulouse, UMR INRA-ENVT Xénobiotiques, 23 Capelles, 31076 Toulouse, France.
J Nutr. 2004 Oct;134(10):2711-6. doi: 10.1093/jn/134.10.2711.
Red meat intake is associated with colon cancer risk. Puzzlingly, meat does not promote carcinogenesis in rat studies. However, we demonstrated previously that dietary heme promotes aberrant crypt foci (ACF) formation in rats given a low-calcium diet. Here, we tested the hypothesis that heme-rich meats promote colon carcinogenesis in rats treated with azoxymethane and fed low-calcium diets (0.8 g/kg). Three meat-based diets were formulated to contain varying concentrations of heme by the addition of raw chicken (low heme), beef (medium heme), or black pudding (blood sausage; high heme). The no-heme control diet was supplemented with ferric citrate and the heme control diet with hemoglobin to match iron and heme concentrations in the beef diet, respectively. After 100 d, colons were scored for ACF and mucin-depleted foci (MDF). Fecal water was assayed for lipoperoxides and cytotoxicity. Only diets with heme promoted the formation of MDF, but all meat diets promoted ACF formation. The number of MDF/colon was 0.55 +/- 0.68 in controls, but 1.2 +/- 0.6 (P = 0.13), 1.9 +/- 1.4 (P < 0.01), and 3.0 +/- 1.2 (P < 0.001) in chicken-, beef-, and black pudding-fed rats. MDF promotion by the high-heme black pudding diet was greater than that by the medium-heme beef diet. The number of ACF/colon was 72 +/- 16 in controls, but 91 +/- 18, 100 +/- 13, and 103 +/- 14 in chicken-, beef-, and black pudding-fed rats (all P < 0.001). ACF and MDF did not differ between rats fed the beef diet and those fed the heme control diet. MDF promotion was correlated with high fecal water lipoperoxides and cytotoxicity (r = 0.65, P < 0.01). This is the first study to show the promotion of experimental carcinogenesis by dietary meat and the association with heme intake.
红肉摄入量与结肠癌风险相关。令人困惑的是,在大鼠研究中肉类并不会促进致癌作用。然而,我们之前证明,在给予低钙饮食的大鼠中,膳食血红素会促进异常隐窝灶(ACF)的形成。在此,我们检验了以下假设:富含血红素的肉类会促进用氧化偶氮甲烷处理并喂食低钙饮食(0.8克/千克)的大鼠发生结肠癌。通过添加生鸡肉(低血红素)、牛肉(中等血红素)或黑布丁(血肠;高血红素)来配制三种以肉类为基础的饮食,使其含有不同浓度的血红素。无血红素对照饮食补充柠檬酸铁,血红素对照饮食补充血红蛋白,以分别匹配牛肉饮食中的铁和血红素浓度。100天后,对结肠进行ACF和黏液缺失灶(MDF)评分。检测粪便水的脂质过氧化物和细胞毒性。只有含血红素的饮食会促进MDF的形成,但所有肉类饮食都会促进ACF的形成。对照组中MDF/结肠的数量为0.55±0.68,但在喂食鸡肉、牛肉和黑布丁的大鼠中分别为1.2±0.6(P = 0.13)、1.9±1.4(P < 0.01)和3.0±1.2(P < 0.001)。高血红素黑布丁饮食对MDF的促进作用大于中等血红素牛肉饮食。对照组中ACF/结肠的数量为72±16,但在喂食鸡肉、牛肉和黑布丁的大鼠中分别为91±18、100±13和103±14(均P < 0.001)。喂食牛肉饮食的大鼠和喂食血红素对照饮食的大鼠之间ACF和MDF没有差异。MDF的促进作用与高粪便水脂质过氧化物和细胞毒性相关(r = 0.65,P < 0.01)。这是第一项表明膳食肉类促进实验性致癌作用以及与血红素摄入量相关的研究。