CARCINOGENESIS: NITROSAMINE FORMATION AND INHIBITION

致癌：亚硝胺的形成和抑制

• 批准号: 3482074
• 负责人: Richard N Loeppky
• 金额: $ 11.1万
• 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/3482074
• 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.

建议的研究作为一个高概率的识别 重要的化学特征，既易患，又有助于 阻断或抑制致癌亚硝胺的快速形成 从某些氮化合物在体内和 环境 在我们的知识中有许多空白， 分子和其他化学因素，导致快速或 明显的亚硝胺形成。 例如，我们不知道， 亚硝胺是如何在化妆品、洗发水和其他 化妆品、金属加工液和烟草。 内源 许多N-亚硝基化合物的形成可能未被发现 因为它们的新陈代谢太快而且可能有害。 我们 我相信，对化学的基本理解， 亚硝化方法，特别是涉及三元氮的亚硝化方法 化合物，可以导致消除或减少 暴露于亚硝胺，从而预防人类癌症。 由三元氮快速生成亚硝胺 含有富电子的叔胺等化合物 芳环，叔脒，和宝石二胺，将是 检查了必要的结构特征， 内源性亚硝化、亚硝酸盐水平、pH值和- SCN浓度。 几种复杂的药物和食物成分 包括利血平、海克替丁、美沙非那林、脒基青霉素和 将筛选Medibazine的致突变性。 吡咯和 将检查含有吡咯的聚合物的能力， 阻断亚硝胺的形成。 酯介导的亚硝化反应， 通过这项研究发现的反应， 对于商业样品中意外的亚硝胺形成， 将进一步阐明。