Effects of 20 months of ozone exposure on lung collagen in Fischer 344 rats.

Fischer 344 rats were exposed to filtered air (controls) or to 0.12, 0.5, or 1.0 ppm of ozone for 6 h/day, 5 days/week, for 20 months. We examined lung collagen deposition and metabolism in tissue from these animals to determine whether chronic exposure of rats to ozone causes pulmonary fibrosis. We observed excess stainable collagen in the centriacinar region of lungs from the rats exposed to 0.5 or 1.0 ppm of ozone. Biochemical analysis indicated a slight, yet significant, excess collagen deposition in the female rats exposed to 0.5 or 1.0 ppm of ozone. Collagen in the lungs of the females also contained relatively more hydroxylysine-derived crosslinks than did lung collagen from age-matched control animals. No excess of type I procollagen mRNA could be appreciated by in situ hybridization in lungs of the rats exposed to 1.0 ppm of ozone for 20 months, although this mRNA was detected in occasional alveolar interstitial cells at 2 months of exposure to ozone under the same protocol. These findings indicate that chronic exposure of rats to ozone causes mild, persistent fibrosis. The significance of these observations with regard to human health risks of chronically inhaling ozone at ambient levels in polluted air remains to be determined.