CARCINOGENESIS: NITROSAMINE FORMATION AND INHIBITION

建议的研究认为识别出 重要的化学特征，既易于发生，也有助于 阻止或抑制致癌亚硝胺的快速形成 体内和体内的某些含氮化合物 环境。我们对这一问题的认识有许多空白 导致快速死亡的分子和其他化学因素 大量亚硝胺的形成。例如，不知道， 亚硝胺是如何在化妆品、洗发水等中形成的 化妆品、金属加工液和烟草。内生性 许多N-亚硝基化合物的形成可能不会被检测到 因为它们的新陈代谢很快，而且可能是有害的。我们 相信对化学的基本理解 亚硝化过程，特别是与三元氮有关的过程 化合物，可以导致消除或减少的方法 暴露在亚硝胺中，从而预防人类癌症。 三元氮气快速生成亚硝胺 含有富含电子的叔胺类化合物 芳环、叔胺和宝石二胺将是 就必要的结构特征和 内源亚硝化作用、亚硝酸盐水平、pH和- SCN浓度。几种复杂的药物和食品成分 包括利血平、己替丁、美非那林、氨诺西林和 将对麦迪巴肼进行诱变性筛查。吡咯和 含有吡咯的聚合物将被检查它们的能力 堵塞亚硝胺地层。酯介导的亚硝化，a 通过这项研究发现的反应，可能是 对于商业样品中无意中形成的亚硝胺， 将进一步阐明。

The proposed research as a high probability of identifying important chemical features which both predispose and serve to block or inhibit the rapid formation of carcinogenic nitrosamines from certain nitrogen compounds both in vivo and in the environment. There are many gaps in our knowledge of the molecular and other chemical factors which lead to rapid or significant nitrosamine formation. It is not know, for example, how nitrosamines are formed in cosmetics, shampoos, other toiletry items, metalworking fluids, and tobacco. Endogenous formation of many N-nitroso compounds may go undetected because of their rapid and possible injurious metabolism. We believe that a fundamental understanding of the chemistry of the nitrosation process, particularly as it relates to ternary nitrogen compounds, can lead to methods for eliminating or decreasing exposure to nitrosamines and thereby prevent human cancer. The rapid formation of nitrosamines from ternary nitrogen compounds including tertiary amines containing an electron rich aromatic ring, tertiary amidines, and gem diamines, will be examined with respect to the necessary structural features and the variables of endogenous nitrosation, nitrite level, pH, and - SCN concentration. Several complex drugs and food constituents including reserpine, hexetidine, methaphenaline, amidinocillin and medibazine will be screened for mutagenicity. Pyrroles and polymers containing pyrroles will be examined for their ability to block nitrosamine formation. Ester mediated nitrosation, a reaction discovered through this research and possibly responsible for inadvertent nitrosamine formation in commercial samples, will be further elucidated.