Kuhnle G G C, Bingham S A
MRC Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 0XY, U.K.
Biochem Soc Trans. 2007 Nov;35(Pt 5):1355-7. doi: 10.1042/BST0351355.
Colorectal cancer is the third most common cancer in developed countries such as the U.K., but incidence rates around the world vary approx. 20-fold. Diet is thought to be a key factor determining risk: red and processed meat, but not white meat or fish, are associated with an increased risk of colorectal cancer. The endogenous formation of N-nitroso compounds is a possible explanation because red and processed meat, but not white meat or fish, cause a dose-dependent increase in faecal ATNCs (apparent total N-nitroso compounds) and the formation of nitroso-compound-specific DNA adducts in humans. Red meat is particularly rich in haem which has been found to promote the endogenous formation of ATNC. Nitrosyl haem and nitroso thiols have been identified as major constituents of both faecal and ileal ATNC with a significant increase in the formation of these compounds following a diet rich in red meat. In vitro incubations show that, under simulated gastric conditions, nitroso thiols are the main species of nitroso compound formed, suggesting that acid-catalysed thionitrosation is the initial step in the endogenous formation of nitroso compounds. Nitrosyl haem and other nitroso compounds can then form under the alkaline and reductive conditions of the small and large bowel.
在英国等发达国家，结直肠癌是第三大常见癌症，但全球发病率约相差20倍。饮食被认为是决定风险的关键因素：红肉和加工肉类而非白肉或鱼类与结直肠癌风险增加有关。N-亚硝基化合物的内源性形成是一种可能的解释，因为红肉和加工肉类而非白肉或鱼类会导致粪便中表观总N-亚硝基化合物（ATNCs）呈剂量依赖性增加，并在人体中形成亚硝基化合物特异性DNA加合物。红肉中血红素含量特别丰富，已发现血红素会促进ATNC的内源性形成。亚硝酰血红素和亚硝基硫醇已被确定为粪便和回肠ATNC的主要成分，食用富含红肉的饮食后，这些化合物的形成会显著增加。体外培养表明，在模拟胃条件下，亚硝基硫醇是形成的主要亚硝基化合物种类，这表明酸催化的硫亚硝化是亚硝基化合物内源性形成的初始步骤。然后，在小肠和大肠的碱性和还原条件下可形成亚硝酰血红素和其他亚硝基化合物。
