Endogenous induction of nitrosamines

为了了解环境中存在的亚硝化反应是否与炎症过程中的亚硝化反应有关，我们用ESR检测了白细胞介素1（IL-1）、肿瘤坏死因子（TNF）和干扰素-γ（IFN-γ）对大鼠血液中NO-血红蛋白（HbNO）的影响，因为亚硝化反应的程度与NO的产生有关。IL-1或TNF单独刺激NO-血红蛋白（HbNO）产生，但IFN-γ单独刺激不刺激，表明两种刺激对NO产生的协同作用。此外，LPS和TNF的组合是更有效的刺激剂HbNO的生产在大鼠比单独。加入IFN-γ的LPS处理的大鼠TNF的释放显着增加。提示IFN-γ增加TNF释放在LPS诱导的大鼠NO生成中起关键作用。在这些实验中，不同的三线高密度结构的HbNO是存在于静脉血，但不是在动脉血。结果表明，随着血红蛋白氧饱和度的降低，三线超精细结构呈线性增强，但随着血红蛋白氧饱和度的恢复，三线超精细结构消失。结果表明，大鼠局灶性脑缺血再灌注后血浆硝酸盐含量升高，HbNO含量增加。此外，我们还用氮的稳定同位素证明了NO是由硝基血管扩张剂代谢产生的。如果环境中存在可亚硝基化的亚硝酸盐，并且如果某人缺乏抗坏血酸，则他可能暴露于由内源性NO形成的亚硝胺的威胁，特别是在炎症的情况下。

To know whcther environmentally existing amins are involved in in vivo nitrosation during inflammation, we studied the effect of interleukin 1 (IL-1) tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) on NO production inrats by detecting NO-hemoglobin (HbNO) in their blood using ESR,since the extent of nitrosation paralleled with NO production. Either IL-1 or TNF alone, but not IFN-gamma alone stimulated NO-hemoglobin (HbNO) generation, demonstrating synorglstic character of both stimuli on NO production. Further, LPS and TNF in combination were more potent stimulator of HbNO production in rats than each alone. Addition of IFN-gamma to the LPS-treated rats increased the TNF release markedly. These suggest that the increase of TNF release by IFN-gamma plays a key role in LPS-trated rats with respect to NO generation. During these experiments, distinct three-line hyperfune structure of HbNO was present in venous blood but not in arterial blood. We cleared that the three-line hyperfine structure intensified lineally with the decrease of oxygen sturation of hemoglobin, but desappeared upon reoxygenation of hemoglobin. We also found that plasma nitrate increases and HbNO appears during rat focal cerebral inschemia and reperfusion. Furthere, we proved using stable isotope of nitrogen that NO generates from nitrovasodilator as a result of metabolism. If nitrosatable amins exist in the environment and if someone is lacking ascorbic acid he may be exposed to the threat of nitrosamine formation by the endogenous NO especially in the case of inflammation.