Patterns of epithelial cell proliferation in the alveoli and in the small airways are well characterized following acute lung injury by ozone, whereas surprisingly little data are available under condition of chronic exposure. However, an understanding of pulmonary epithelial cell proliferation in response to a chronic ozone challenge might help to explain some recent and apparently paradox observations: in one mouse strain, the A mouse, ozone appears to enhance the development of chemically induced lung tumors, provided the animals are exposed to ozone first, followed by exposure to urethan. On the other hand, the response of alveolar epithelial cells having undergone transformation into adenomas is different; ozone inhibits their further growth and development. In a different mouse strain, the SWR mouse, no such responses are seen. It is proposed to examine the hypothesis that this observation can be explained by patterns of cell proliferation during and following ozone exposure. We will examine, with autoradiographic techniques, whether in the lungs of A mice, chronic ozone exposure will increase proliferative activity and number of the normal alveolar epithelial cells, whereas the response of an altered epithelial cell population, forming urethan-induced adenomas, will consist in an ozone-induced slowed down growth pattern. The findings in the A mice will be compared with SWR mice where ozone does not appear capable to elicit the same response as in A mice and, therefore, might produce dissimilar changes in cell proliferative patterns as a response to chronic exposure.
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