Nitrate is converted to nitrite in the human body and subsequently can react with amines and amides in the gastrointestinal tract to form N-nitroso compounds (NOCs), which are known to be carcinogenic in animals. Humans can be exposed to nitrate via consumption of drinking water and diet, especially green leafy vegetables and cured meat. The contribution of nitrate from drinking water in combination with meat intake has not been investigated thoroughly. Therefore, in the present pilot study, we examined the effect of nitrate from drinking water, and its interaction with the consumption of white and processed red meat, on the endogenous formation of NOCs, taking into account the intake of vitamin C, a nitrosation inhibitor. Twenty healthy subjects were randomly assigned to two groups consuming either 3.75 g/kg body weight (maximum 300 g per day) processed red meat or unprocessed white meat per day for two weeks. Drinking water nitrate levels were kept low during the first week (< 1.5 mg/L), whereas in week 2, nitrate levels in drinking water were adjusted to the acceptable daily intake level of 3.7 mg/kg bodyweight. At baseline, after 1 and 2 weeks, faeces and 24 h urine samples were collected for analyses of nitrate, apparent total N-nitroso compounds (ATNC), compliance markers, and genotoxic potential in human colonic Caco-2 cells. Urinary nitrate excretion was significantly increased during the high drinking water nitrate period for both meat types. Furthermore, levels of compliance markers for meat intake were significantly increased in urine from subjects consuming processed red meat (i.e. 1-Methylhistidine levels), or unprocessed white meat (i.e. 3-Methylhistidine). ATNC levels significantly increased during the high drinking water nitrate period, which was more pronounced in the processed red meat group. Genotoxicity in Caco-2 cells exposed to faecal water resulted in increased genotoxicity after the interventions, but results were only significant in the low drinking water nitrate period in subjects consuming processed red meat. Furthermore, a positive correlation was found between the ratio of nitrate/vitamin C intake (including drinking water) and the level of ATNC in faecal water of subjects in the processed red meat group, but this was not statistically significant. Drinking water nitrate significantly contributed to the endogenous formation of NOC, independent of the meat type consumed. This implies that drinking water nitrate levels should be taken into account when evaluating the effect of meat consumption on endogenous formation of NOC. Dutch Trialregister: 29707 . Registered 19th of October 2018. Retrospectively registered.

中文翻译：

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饮用水中硝酸盐含量高对健康志愿者肉类摄入中表观N-亚硝基化合物内源性形成的影响

硝酸盐在人体中转化为亚硝酸盐，随后可与胃肠道中的胺和酰胺反应形成N-亚硝基化合物（NOC），众所周知，N-亚硝基化合物对动物具有致癌性。食用饮用水和饮食，尤其是绿叶蔬菜和腌制肉类，可能使人暴露于硝酸盐中。饮用水中硝酸盐与肉类摄入量的关系尚未得到彻底研究。因此，在本试验研究中，我们考虑了摄入亚硝化抑制剂维生素C的情况，研究了饮用水中硝酸盐的影响及其与食用白肉和加工红肉的相互作用对内源性NOC形成的影响。 。二十名健康受试者被随机分为两组，每组消耗3。每天75克/千克体重（每天最多300克）加工的红肉或未经加工的白肉，持续两周。在第一周，饮用水中的硝酸盐含量保持较低水平（<1.5 mg / L），而在第2周中，饮用水中的硝酸盐含量被调整为每天可接受的3.7 mg / kg体重。在基线时，在第1和2周后，收集粪便和24小时尿液样本，以分析硝酸盐，表观总N-亚硝基化合物（ATNC），顺应性标志物和人结肠Caco-2细胞的遗传毒性潜力。在两种硝酸盐的高饮用水硝酸盐期间，尿中硝酸盐的排泄显着增加。此外，食用加工过的红肉的受试者的尿液中肉类摄入量的顺应性标记水平显着提高（即1-甲基组氨酸水平），或未经加工的白肉（即3-甲基组氨酸）。在高饮用水硝酸盐时期，ATNC水平显着增加，在加工的红肉组中更为明显。干预后，暴露于粪便水的Caco-2细胞的遗传毒性导致遗传毒性增加，但结果仅在食用加工红肉的受试者的硝酸盐含量低的饮水期中显着。此外，在加工红肉组的受试者的粪便水中硝酸盐/维生素C摄入量的比率（包括饮用水）与ATNC含量之间呈正相关，但在统计学上无统计学意义。饮用水中的硝酸盐显着促进了NOC的内源性形成，而与所食用的肉类无关。这意味着在评估肉食对NOC内源性形成的影响时，应考虑饮用水中硝酸盐的含量。荷兰试验注册：29707。已于2018年10月19日注册。已追溯注册。