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牛肉促进二甲基肼诱导的结直肠癌发生生物标志物的作用受到膳食钙的抑制。

Beef meat promotion of dimethylhydrazine-induced colorectal carcinogenesis biomarkers is suppressed by dietary calcium.

作者信息

Pierre Fabrice, Santarelli Raphaëlle, Taché Sylviane, Guéraud Françoise, Corpet Denis E

机构信息

UMR1089 Xénobiotiques, INRA-ENVT, 23 ch Capelles, Toulouse, France.

出版信息

Br J Nutr. 2008 May;99(5):1000-6. doi: 10.1017/S0007114507843558. Epub 2007 Oct 22.

Abstract

Red meat consumption is associated with increased risk of colorectal cancer. We have previously shown that haemin, Hb and red meat promote carcinogen-induced preneoplastic lesions: aberrant crypt foci (ACF) and mucin-depleted foci (MDF) in rats. We have also shown that dietary Ca, antioxidant mix and olive oil inhibit haemin-induced ACF promotion, and normalize faecal lipoperoxides and cytotoxicity. Here we tested if these strategies are effective also against red meat promotion in dimethylhydrazine-induced rats. Three diets with 60 % beef meat were supplemented with calcium phosphate (31 g/kg), antioxidant agents (rutin and butylated hydroxyanisole, 0.05 % each) and olive oil (5 %). ACF, MDF, faecal water cytotoxicity, thiobarbituric acid reactive substances (TBARS) and urinary 1,4-dihydroxynonane mercapturic acid (DHN-MA) were measured. Beef meat diet increased the number of ACF (+30 %) and MDF (+100 %) (P < 0.001), which confirms our previous findings. Promotion was associated with increased faecal water TBARs ( x 4) and cytotoxicity ( x 2), and urinary DHN-MA excretion ( x 15). Ca fully inhibited beef meat-induced ACF and MDF promotion, and normalized faecal TBARS and cytotoxicity, but did not reduce urinary DHN-MA. Unexpectedly, high-calcium control diet-fed rats had more MDF and ACF in the colon than low-Ca control diet-fed rats. Antioxidant mix and olive oil did not normalize beef meat promotion nor biochemical factors. The results confirm that haem causes promotion of colon carcinogenesis by red meat. They suggest that Ca can reduce colorectal cancer risk in meat-eaters. The results support the concept that toxicity associated with the excess of a useful nutrient may be prevented by another nutrient.

摘要

食用红肉与结直肠癌风险增加有关。我们之前已经表明,血红素、血红蛋白和红肉会促进致癌物诱导的大鼠癌前病变:异常隐窝病灶(ACF)和黏液缺失病灶(MDF)。我们还表明,膳食钙、抗氧化剂混合物和橄榄油可抑制血红素诱导的ACF进展,并使粪便脂质过氧化物和细胞毒性恢复正常。在此,我们测试了这些策略是否也能有效对抗二甲基肼诱导的大鼠中红肉的促癌作用。三种含60%牛肉的饮食分别补充了磷酸钙(31克/千克)、抗氧化剂(芦丁和叔丁基对羟基茴香醚,各0.05%)和橄榄油(5%)。测量了ACF、MDF、粪便水细胞毒性、硫代巴比妥酸反应性物质(TBARS)和尿1,4 - 二羟基壬烷巯基尿酸(DHN - MA)。牛肉饮食增加了ACF数量(+30%)和MDF数量(+100%)(P < 0.001),这证实了我们之前的发现。促癌作用与粪便水TBARs增加(×4)、细胞毒性增加(×2)以及尿DHN - MA排泄增加(×15)相关。钙完全抑制了牛肉诱导的ACF和MDF进展,并使粪便TBARS和细胞毒性恢复正常,但并未降低尿DHN - MA。出乎意料的是,高钙对照饮食喂养的大鼠结肠中的MDF和ACF比低钙对照饮食喂养的大鼠更多。抗氧化剂混合物和橄榄油并未使牛肉的促癌作用及生化因素恢复正常。结果证实血红素会导致红肉促进结肠癌发生。它们表明钙可以降低肉食者患结直肠癌的风险。这些结果支持了这样一种概念,即一种有益营养素过量相关的毒性可能会被另一种营养素预防。

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