CARCINOGENESIS: NITROSAMINE FORMATION AND INHIBITION

致癌：亚硝胺的形成和抑制

• 批准号: 3482071
• 负责人: Richard N Loeppky
• 金额: $ 13.46万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-02-01 至 1991-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3482071
• 关键词: alkaloids; antibacterial agents; antihistamines; carcinogen testing; carcinogenesis inhibitor; chemical carcinogen; chemical carcinogenesis; chemical reaction; chemical structure function; drug adverse effect; drug carcinogenesis; environment related neoplasm /cancer; environmental toxicology; food contamination; gas chromatography; high performance liquid chromatography; indoles; mass spectrometry; mutagen testing; nitrogen compounds; nitrosamines; nitroso compounds; nuclear magnetic resonance spectroscopy; nutrition related tag; occupational hazard; polymers; pyrroles; quaternary ammonium compound; sedative /hypnotic; skin; stoichiometry; tertiary amine; toxicant screening; toxin metabolism

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.

拟议的研究很有可能识别出 重要的化学特征，既倾向于并有助于 阻断或抑制致癌亚硝胺的快速形成 来自体内和环境中的某些氮化合物 环境。 我们的知识还有很多差距 分子和其他化学因素导致快速或 大量亚硝胺形成。 不知道，例如， 化妆品、洗发水和其他产品中亚硝胺是如何形成的 盥洗用品、金属加工液和烟草。 内源性 许多 N-亚硝基化合物的形成可能未被检测到 因为它们的新陈代谢快速且可能有害。 我们 相信对化学的基本了解 亚硝化过程，特别是与三元氮相关的过程 化合物，可以导致消除或减少的方法 接触亚硝胺，从而预防人类癌症。 三元氮快速形成亚硝胺 包括含有富电子的叔胺的化合物 芳香环、叔脒和偕二胺，将 检查必要的结构特征和 内源亚硝化、亚硝酸盐水平、pH 值和 - SCN浓度。 几种复杂的药物和食品成分 包括利血平、己替丁、甲基苯那林、脒西林和 将筛选麦地巴嗪的致突变性。 吡咯和 将检查含有吡咯的聚合物的能力 阻止亚硝胺的形成。 酯介导的亚硝化， 通过这项研究发现的反应可能是其原因 对于商业样品中无意中形成的亚硝胺， 将进一步阐明。