SINGLET OXYGEN AND LUNG PATHOGENESIS

单线态氧，O2-，已被确定为潜在的大气 氧化剂。虽然它在大气中的稳态浓度很低， O2-的寿命足够长，可以与烯烃和 多环烃形成有毒或潜在的诱变化合物。 O2-的寿命相对较长，表明它可能通过 吸气。目前的研究表明，O2-可能是在肺中形成的， 例如通过臭氧与生物底物的反应。在肺部， 一个引发事件可以导致许多生物分子的氧化。O2- 会在气管、支气管上皮产生微妙的化学变化， 肺泡表面活性物质和巨噬细胞可易感多种 病理情况。O2-攻击不饱和脂肪酸部分 脂类通过“烯”反应形成过氧化氢； 丙二醛可以通过二次反应生成。过氧化氢是 已知会导致肺部炎症、浮肿和出血。丙二醛 而脂质环氧化物可以起到烷化剂的作用，最终导致 癌症。O2-参与了导致这些的化学事件 生物效应需要用独特的声音来证明。 这项研究将(1)继续调查实验室产生的 异相光敏化和额外的O2-形成 环境反应，(2)用模型膜研究O2-的反应 系统，即合成脂质的脂质体，以确定化学物质 O2-引发生物损伤的机制，以及(3)在 仓鼠气管上皮的体外暴露。该计划的总体目标 研究是为了确定大气中的 产生的O2-和一些可归因于空气的不良健康影响 污染。

Singlet oxygen, O2-, has been identified as a potential atmospheric oxidant. Although its steady state concentration in the atmosphere is low, O2- is sufficiently long-lived to react with pollutants such as olefins and polycyclic hydrocarbons to form toxic or potentially mutagenic compounds. The relatively long lifetime of O2- suggests that it may reach the lung by inhalation. Current research indicates that O2- may be formed in the lung, e.g., by the reaction of ozone with biological substrates. In the lung, one initiating event can lead to the oxidation of many biomolecules. O2- can produce subtle chemical changes in the tracheal bronchial epithelium, alveolar surfactant, and macrophages that can predispose to various pathological conditions. O2- attacks the unsaturated fatty acid moieties of lipids to form hydroperoxides via the "ene" reaction; lipid epoxides and malonylaldehyde may form by secondary reactions. The hydroperoxides are known to cause lung inflammation, edema, and hemorrhaging. Malonylaldehyde and lipid epoxides can act as alkylating agents and ultimately lead to cancer. The involvement of O2- in the chemical events that lead to these biological effects needs to be uniquivocally demonstrated. The research will (1) continue to investigate the laboratory generation of O2- by heterogeneous photosensitization and additional O2-forming environmental reactions, (2) study the reaction of O2- with model membrane systems, i.e., liposomes of synthetic lipids, to determine the chemical mechanisms by which O2- initiates biological damage, and (3) complete in vitro exposure of hamster tracheal epithelium. The overall goal of the research is to determine if there is a link between atmospherically generated O2- and some of the adverse health effects attributed to air pollution.