O3 AND MODULATING CR INDUCED LUNG IMUNOTOXICITY

焊接，这是一种通常用于建筑和几个 制造业，呈现出局部化的集中氛围 含有几种可溶/微粒金属和气体给焊工。许多 这些成分中的一种已被证明是致癌物质/免疫毒素 在体外和实验动物模型中。不断增长的 流行病学证据表明，接触焊接烟雾， 最具体地说，那些含有铬(Cr)的化合物与 肺癌发病率增加。某些形式的铬是致癌物质 在实验条件下，它是唯一的吸入剂。 然而，其他烟气成分对铬的去除和排放的影响 对肺部的毒性仍不清楚。 臭氧(O3)是焊接过程中释放的一种主要气体。许多活体研究 体外实验表明，臭氧也可以改变肺的清除功能 作为巨噬细胞/淋巴细胞的细胞性和功能活性， 尤其是那些参与肿瘤监测的人。它的目的是 研究目的是确定同时吸入臭氧和铬是否 (在不同的可溶状态)改变了铬在肺中的保留， 影响肺肿瘤监视机制的方式不同于 当单独吸入铬时可以观察到这一点。 据推测，臭氧会引起肺部的变化，从而导致 有利于铬致肺癌发病率增加的条件。 为证实这一点而提出的具体目标是：(1)论证 同时吸入臭氧可延长铬在肺内的持续期，并 还能延长细胞内六价铬的寿命 肺细胞外液，以及(2)确定臭氧是否 结合铬本身产生的那些效应进行调制， 对肿瘤监测至关重要的肺部免疫学参数。对这件事 结束，分析体内对肺肿瘤形成的耐药性，评估 肺巨噬细胞/自然杀伤细胞细胞毒活性、细胞因子 产生、溶瘤介体释放和表达/功能 关键的细胞表面受体，将被执行。 这些研究的结果将有助于更好地定义这些机制 暴露在焊接烟雾中后，潜在的宿主免疫能力发生了变化， 一种重要的职业污染物混合物。这些结果可能会为我们提供一些 年臭氧和铬的允许暴露量的修订依据 焊接油烟，从而更好地保护眼前和长期的健康 尤其是建筑工人，以及所有工业焊工 将军。

Welding, a process commonly used in construction and in several manufacturing industries, presents a localized concentrated atmosphere containing several soluble/particulate metals and gases to welders. Many of these components have been shown to be carcinogens/immunotoxicants in vitro and in experimental animal models. A growing body of epidemiological evidence has indicated that exposure to welding fumes, most specifically those containing chromium (Cr), correlates with increased incidence of lung cancer. Certain forms of Cr are carcinogens under experimental conditions where it is the sole inhaled agent. However, the impact of other fume components upon Cr disposition and toxicity in the lung is still unclear. Ozone (O3) is a major gas released during welding. Many studies in vivo and in vitro have shown that O3 can alter lung clearance functions as well as macrophage/lymphocyte cellularity and functional activities, particularly those involved in tumor surveillance. The object of this study is to ascertain whether the simultaneous inhalation of O3 with Cr (in different soluble states) alters the retention of the Cr in the lung, and affects lung tumor surveillance mechanisms in a manner different from that observed when Cr is inhaled alone. It is hypothesized that O3 induces changes in the lung which give rise to conditions favorable to an increased incidence of Cr-induced lung cancers. The specific aims proposed to substantiate this are: (1) to demonstrate that simultaneous inhalation of O3 prolongs Cr persistence in the lung and also results in an increased longevity for hexavalent Cr within cells and extracellular fluids of the lung, and (2) to ascertain whether O3 modulates, in conjunction with those effects derived from Cr itself, parameters of lung immunology critical to tumor surveillance. To this end, analyses of in vivo resistance to lung tumor formation, assessments of pulmonary macrophage/natural killer cell cytotoxic activity, cytokine generation, oncolytic mediator release, and expression/functionality of crucial cell surface receptors, will be performed. The results from these studies will aid in better defining the mechanisms underlying altered host immunocompetence after exposure to welding fumes, an important occupational pollutant mixture. The results may provide some basis for revisions in the permissible levels of exposures to O3 and Cr in welding fumes, so as to better protect the immediate and long-term health of construction workers in particular, and all industrial welders in general.