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，可以与烯烃等污染物反应， 多环碳氢化合物形成有毒或潜在的致突变化合物。 O2-的相对较长的寿命表明它可能通过以下方式到达肺部： 吸入。 目前的研究表明，O2-可能在肺中形成， 例如，在一个实施例中，通过臭氧与生物基质的反应。 在肺部， 一个引发事件可导致许多生物分子的氧化。 O2- 可以在气管支气管上皮细胞中产生细微的化学变化， 肺泡表面活性物质和巨噬细胞，可以使各种 病理条件。 O2-攻击不饱和脂肪酸部分 脂质通过“烯”反应形成氢过氧化物;脂质环氧化物和 可以通过次级反应形成丙二醛。 氢过氧化物是 已知会导致肺部炎症水肿和水肿。 丙二醛 和脂质环氧化物可作为烷基化剂并最终导致 癌 O2-参与导致这些的化学事件 生物效应需要明确证明。 该研究将（1）继续研究实验室生成的 O2-通过非均相光敏化和额外的O2-形成 环境反应，（2）研究O2-与模型膜的反应 系统，即，合成脂质体，以确定化学 O2-引发生物损伤的机制，以及（3）完成在 仓鼠气管上皮的体外暴露。 的总体目标 研究的目的是确定大气中的 产生的O2-和一些不利的健康影响归因于空气 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.