O3 AND MODULATING CR INDUCED LUNG IMUNOTOXICITY

O3 和调节 CR 诱导的肺部免疫毒性

• 批准号: 2155665
• 负责人: Richard B Schlesinger
• 金额: $ 29.29万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-02-01 至 1998-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2155665
• 关键词: alveolar macrophages; atomic absorption spectrometry; chemical carcinogenesis; chromium; cocarcinogen; cytokine; cytotoxicity; diagnostic respiratory lavage; environmental toxicology; industry; laboratory rat; lung neoplasms; natural killer cells; neoplasm /cancer epidemiology; neoplasm /cancer immunology; nitric oxide; occupational disease /disorder; occupational hazard; ozone; pollution related respiratory disorder; toxicant interaction

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.

焊接，一种通常用于建筑和几个领域的工艺， 制造业，呈现出局部集中的氛围 含有几种可溶性/颗粒金属和气体。 许多 这些成分中的一种已被证明是致癌物/免疫毒物， 体外和实验动物模型。 越来越多的 流行病学证据表明，接触焊接烟雾， 最特别是那些含有铬（Cr），与 肺癌的发病率增加。 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，其他烟雾成分对铬沉积的影响， 肺部毒性尚不清楚。 臭氧（O3）是焊接过程中释放的主要气体。 许多体内研究 体外实验表明，O3也可以改变肺清除功能， 如巨噬细胞/淋巴细胞的细胞结构和功能活性， 特别是那些参与肿瘤监测的人。 这个的目的是 研究的目的是确定同时吸入O3和Cr (in不同的可溶状态）改变了Cr在肺中的保留， 并以不同于 当单独吸入Cr时观察到的。 据推测，O3诱导肺的变化，引起 有利于铬诱发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）证明 同时吸入O3会使Cr在肺中持续存在， 还导致电池内六价铬的寿命增加， 肺的细胞外液，和（2）以确定是否O3 调节，连同来自铬本身的那些效应， 肺免疫学参数对肿瘤监测至关重要。 本 最后，分析体内对肺肿瘤形成的抗性，评估 肺巨噬细胞/自然杀伤细胞的细胞毒活性，细胞因子 产生、溶瘤介质释放和表达/功能 关键的细胞表面受体，将进行。 这些研究的结果将有助于更好地确定机制 暴露于焊接烟雾后宿主免疫活性的潜在改变， 一种重要的职业污染物混合物。 结果可能会提供一些 修订O3和Cr容许暴露水平的依据， 焊接烟尘，从而更好地保护眼前和长远的健康 特别是建筑工人，以及所有工业焊工， 将军