TOBACCO SMOKE AND COMBUSTION TOXICOLOGY

烟草烟雾和燃烧毒理学

• 批准号: 2215885
• 负责人: WILLIAM A PRYOR
• 金额: $ 15.64万
• 依托单位: LOUISIANA STATE UNIV A&M COL BATON ROUGE
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-06-01 至 1996-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2215885
• 关键词: DNA damage; alpha 1 antitrypsin; catechols; elastases; electron spin resonance spectroscopy; free radical oxygen; laboratory rat; mass spectrometry; nitric oxide; nitrogen oxides; nuclear magnetic resonance spectroscopy; tobacco; toxicant interaction

Tobacco smoke contains high concentrations of oxidants and free radicals and increases the oxidative stress on the lung. This proposal outlines studies of the molecular mechanisms involved in chemical reactions caused by aqueous extracts of cigarette smoke and tar. Extracts of whole (i.e., unfiltered) smoke, of cigarette tar, and of gas-phase smoke contain different compounds and react differently with bio-targets; therefore, this proposal includes studies of all three. In addition, studies of extracts of both mainstream smoke and environmental tobacco smoke are proposed. Extracts of cigarette tar contain high concentrations of a free radical, identified by electron spin resonance (ESR) methods as a semiquinone (QH.). This QH. radical can reduce dioxygen to give superoxide, leading to hydrogen peroxide and the hydroxyl radical. In addition, smoke extracts contain nitric oxide (NO), nitrogen dioxide (NO2), peroxynitrous (HO-ON=O) and peroxynitric acids (HO-ONO2) and their esters, organic peroxides, and aldehydes. Any or all of these species could be involved in smoking-induced pathology, and studies of these compounds also are proposed. Two bio-target molecules are chosen as models for study. (i) The antiprotease alpha-1-proteinase inhibitor (a1PI) is thought to be involved in protecting lung tissue from changes leading to emphysema. The effects of smoke extracts on a1PI and on Met-10, a decapeptide that models the active site of a1PI, will be studied. (ii) The species responsible for smoke extract-induced nicking of DNA in rat alveolar macrophages, spleen cells and thymocytes will be determined. The possibility of base-sequence specificity of the nicking will be examined using plasmid DNA fragments. The radical chemistry of smoke extracts is duplicated by aged solutions of catechol. Both smoke extracts and these aged catechol solutions are used to determine whether the tar radical binds to DNA prior to causing nicks.

烟草烟雾含有高浓度的氧化剂和自由基 并增加肺部的氧化应激。该提案概述了 研究引起化学反应的分子机制 用香烟烟和焦油的水提取物。整体提取（即 未过滤的）烟雾，香烟焦油和气相烟雾含有 不同的化合物和与生物靶标有不同的反应。所以， 该建议包括对这三个的研究。另外，研究 主流烟雾和环境烟草烟雾的提取物是 建议的。香烟的提取物含有高浓度的免费 自由基，通过电子自旋共振（ESR）方法鉴定为A 半喹酮（QH。）。这个QH。激进可以减少二氧化物以提供 超氧化物，导致过氧化氢和羟​​基自由基。在 此外，烟雾提取物含有一氧化氮（NO），二氧化氮 （NO2），过氧亚硝酸（HO-ON = O）和过氧亚硝酸（HO-ONO2）及其 酯，有机过氧化物和醛。这些物种中的任何一个或全部 可能参与吸烟引起的病理学，并研究这些 还提出了化合物。 选择两个生物目标分子作为研究模型。 （i） 抗蛋白酶α-1-蛋白酶抑制剂（A1PI）被认为涉及 在保护肺组织免受导致肺气肿的变化方面。效果 在A1PI和Met-10上的烟雾提取物，这是一种模拟的二肽 将研究A1PI的活跃部位。 （ii）负责的物种 大鼠肺泡巨噬细胞中的烟雾提取物引起的DNA迹 将确定细胞和胸腺细胞。基础序列的可能性 将使用质粒DNA片段检查划痕的特异性。 烟提取物的根本化学通过老化的溶液复制 儿茶酚。使用烟雾提取物和这些老化的儿茶酚解决方案 确定焦油自由基在引起划痕之前是否与DNA结合。