Diet-induced endogenous formation of nitroso compounds in the GI tract
Diet-induced endogenous formation of nitroso compounds in the GI tract
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DOI：
10.1016/j.freeradbiomed.2007.03.011
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发表时间：
2007-10-01
影响因子：
7.4
通讯作者：
Bingham, Sheila A.
中科院分区：
文献类型：
--
作者：
Kuhnle, Gunter G. C.;Story, Giles W.;Bingham, Sheila A.
红肉或加工肉，而不是白肉或鱼，与结直肠癌有关。亚硝基化合物的内源性形成是一种可能的解释，因为红肉或加工肉--而不是白肉或鱼--会导致粪便中表观总N-亚硝基化合物(ATNC)的剂量依赖性增加和亚硝基化合物特异性DNA加合物的形成。红肉中尤其富含血红素，也有研究发现，血红素对ATNC的形成有促进作用。为了研究ATNC形成的潜在机制，分析了进食高红肉或素食的志愿者的粪便和回肠样本中亚硝酸铁、亚硝硫醇和血红素的含量。为了模拟胃内的过程，食物匀浆和血红蛋白在模拟胃条件下孵育。与素食相比，高红肉饮食后回肠和粪便中的亚硝酰铁和亚硝硫醇显著增加(p<；0.0001)；在回肠(p<；0.0001)和粪便(p<；0.001)中检测到的亚硝酰铁明显多于亚硝硫醇。粪便亚硝酸铁与亚铁血红素的强相关性(0.776；p<；0.0001)表明亚硝酸亚铁是亚硝酸铁的主要来源，电子自旋共振证实了高红肉饮食后粪便样品中亚硝酸亚铁的存在。在模拟胃条件下，亚硝基化合物主要生成亚硝基硫醇，这表明亚硝基化合物内源形成的初始步骤是酸催化的硫亚硝化反应。亚硝基、亚铁血红素和其他亚硝基化合物可以在小肠和大肠的碱性和还原条件下形成。(C)2007 Elsevier Inc.保留所有权利。
Red or processed meat, but not white meat or fish, is associated with colorectal cancer. The endogenous formation of nitroso compounds is a possible explanation, as red or processed meat-but not white meat or fish-causes a dose-dependent increase in fecal apparent total N-nitroso compounds (ATNC) and the formation of nitroso-compound-specific DNA adducts. Red meat is particularly rich in heme and heme has also been found to promote the formation of ATNC. To investigate the underlying mechanism of ATNC formation, fecal and ileal samples of volunteers fed a high red meat or a vegetarian diet were analyzed for nitrosyl iron, nitrosothiols, and heme. To simulate the processes in the stomach, food homogenates and hemoglobin were incubated under simulated gastric conditions. Nitrosyl iron and nitrosothiols were significantly (p < 0.0001) increased in ileal and fecal samples after a high red meat diet compared with a vegetarian diet; significantly more nitrosyl iron than nitrosothiols was detectable in ileal (p < 0.0001) and fecal (p < 0.001) samples. The strong correlation between fecal nitrosyl iron and heme (0.776; p < 0.0001) suggested that nitrosyl heme is the main source of nitrosyl iron, and ESR confirmed the presence of nitrosyl heme in fecal samples after a high red meat diet. Under simulated gastric conditions, mainly nitrosothiols were formed, suggesting that acid-catalyzed thionitrosation is the initial step in the endogenous formation of nitroso compounds. Nitrosyl heme and other nitroso compounds can then form under the alkaline and reductive conditions of the small and large bowel. (c) 2007 Elsevier Inc. All rights reserved.