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abstractDetail/abstract/ 2323/report/0 Oxidant Air Pollutants and Lung Cancer: An Animal Model


Ozone and nitrogen dioxide are highly reactive oxidant gases that are derived from the combustion of fossil fuels and the atmospheric transformation of these combustion products. The U.S. Environmental Protection Agency sets National Ambient Air Quality Standards (NAAQS) for these and other pollutants largely on the basis of scientific data documenting their effects on lung structure, function, and response to infectious agents. A major unanswered question is whether or not exposure to oxidant air pollutants contributes to lung cancer. Small cell lung cancer, a highly malignant form of cancer, represents 25% of human lung cancers. Small cell lung tumors are composed primarily of cells with neuroendocrine characteristics. In the past, it has been difficult to investigate the role of environmental factors in the pathogenesis of small cell lung cancer because of the lack of a suitable animal model. However, an animal model for neuroendocrine lung cancer appeared to have been developed when Drs. Schuller, Witschi, and colleagues reported that hamsters developed neuroendocrine cell tumors when they were treated with the chemical carcinogen, diethylnitrosamine (DEN), while inhaling 70% oxygen. The investigators proposed that exposure to high oxygen concentrations (hyperoxia) caused neuroendocrine cells to proliferate and that the dividing cells were susceptible to tumor induction by DEN. Because exposure to both ozone and nitrogen dioxide also causes proliferation of lung cells, including neuroendocrine cells, the researchers suggested that these pollutants could mimic the effects of high oxygen exposures in tumor development. The Health Effects Institute sponsored the present study to examine whether exposure to ozone or nitrogen dioxide enhances the development of tumors induced by DEN, particularly neuroendocrine tumors, in the respiratory tract of hamsters. Approach: Dr. Witschi exposed hamsters continuously to 0.8 ppm ozone for 16 weeks, or 15 ppm nitrogen dioxide for 16 or 24 weeks, or filtered air. The concentrations of the oxidant gases were much higher than those found in ambient air. However, the objective of the study was to determine whether the pollutants had any effects on lung tumor development under extreme conditions before testing ambient levels. Animals also received injections of DEN or saline twice each week. Hamsters exposed to 65% oxygen and injected with DEN were to serve as positive controls. Animals were killed after 16, 24, or 32 weeks, and various tissues were examined by the pathologists, Drs. Schuller and Breider, for neoplastic lesions (carcinomas, adenomas, papillary polyps) and nonneoplastic lesions (hyperplasia and necrosis).