Reaction of rat lungs to inhaled chrysotile asbestos following acute and subchronic exposures.

Inhalation of asbestos fibers can cause fibrotic and neoplastic diseases in the lung. The early in vivo interactions between fibers and lung tissue that initiate these diseases have received little study. Male and female Fischer 344 rats were placed in inhalation chambers and exposed to 9.06 +/- 1.83 mg/m3 (average respirable mass) of chrysotile asbestos for 1 hr, 1 day, 7 hr/day for 5 days, or 5 days/week for 3 months. Qualitative examination of the tissue showed that, after 1 day, fibers were found not only in the alveolar macrophages, but also in the epithelium and interstitium of the alveolar region. After 3 months, numerous fibers were present in the epithelium and interstitium. Morphometric analysis of this tissue showed that these compartments were also the most significantly changed as a result of asbestos exposure. The majority of epithelial changes were attributable to a 57% increase in the number of type II cells and a 90% increase in their average cell volume. The interstitial cell population increased 58% with a 40% increase in the average cell volume. There was no significant increase in the volume of noncellular interstitium. A morphologic characterization of the interstitial cells showed that interstitial macrophages accounted for almost the entire increase in this population and that 88% of the fiber-containing cells were macrophages. Several interstitial macrophages contained membrane-bound inclusions which were shown by x-ray energy spectrometry to be microcalcifications. They were composed of rings of calcium phosphate granules around asbestos fibers. These microcalcifications may indicate sublethal cell injury caused by the presence of asbestos fibers in the cell cytoplasm. Fibers which enter but do not kil alveolar cells may be an essential component for the pathogenesis of lung disease caused by asbestos inhalation.