The human lung is exposed to a mixture of ambient pollutants which may pose a serious threat to human health. Evidence suggests that exposure to airborne particulate metal contaminants and gaseous pollutants, such as ozone (03) alters the immune response. Alveolar macrophages (AM), the main defense of the deep lung, appear to possess anti-tumor activity; ambient pollutants which impair this function may lead to the development and metastasis of cancer. This toxicological study is proposed to evaluate the effects of inhaled 03 and respirable PbO or CdO, alone and in combination, on the rabbit AM tumoricidal activity. Alterations in macrophage functions shown to be important in macrophage anti-tumor activity, namely, phagocytosis, mobility, chemotaxis, receptor cell modulation, tumor cell binding and reactive oxygen production will be assessed to determine possible mechanisms by which pollutant(s) may lead to impairment of macrophage tumoricidal activity. The extent to which changes in these specific functional and biochemical activities, may occur without affecting tumoricidal activity, will also be examined. Little is known of the synergistic effects of ambient pollutant mixtures or their potential mechanism(s). This study combines in vivo exposures with in vitro bioassays and thus offers the unique opportunity to examine effects of real world exposures and possible cellular mechanisms responsible for the effects in a single study.
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| Zelikoff, J T; Parsons, E; Schlesinger, R B (1993) Inhalation of particulate lead oxide disrupts pulmonary macrophage-mediated functions important for host defense and tumor surveillance in the lung. Environ Res 62:207-22 |
| Zelikoff, J T; Kraemer, G L; Vogel, M C et al. (1991) Immunomodulating effects of ozone on macrophage functions important for tumor surveillance and host defense. J Toxicol Environ Health 34:449-67 |
