O3 AND MODULATING CR INDUCED LUNG IMUNOTOXICITY

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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.