Clara-cell hyperplasia after quartz and coal-dust instillation in rat lung

Bronchiolo-alveolar hyperplasia of type II cells in rat lungs after particl e exposure is a well-known preneoplastic lesion. The Clara cell, stem cell of the bronchiolar epithelium and the main carrier of cytochrome P-450 isoe nzyme system in the lung, has barely been evaluated with regard to this eff ect. The aim of this study was to examine Clara-cell hyperplasia after part icle exposure and to characterize cell proliferation and its normal functio n. Female Wistar rats were intratracheally instilled with coal dust samples of variable quartz content, quartz ( DQ12), titanium dioxide, or saline so lution containing 0.5% Tween 80. After 126-129 wk, all coal mine dust- and quartz-exposed animals developed Clara-cell hyperplasia: up to 0.48% of the total lung area, which was significantly increased compared to titanium di oxide ( p < .05) and control ( p < .03) animals. Proliferation and hyperpla sia of bronchiolar Clara cells by coal dusts was independent of their quart z content. The lack of proliferating cell nuclear antigen staining in most of the hyperplastic Clara cells suggests that following damage of alveolar epithelial cells, Clara cells migrate in and remodulate the alveolar epithe lium. After the migration they keep their function in the xenobiotic metabo lism, as shown by expansion of CYP2E1 active Clara cells. The minor develop ment of Clara-cell hyperplasia in titanium dioxide-treated rats indicates t hat this is not a general particle effect, and is possibly due to its lower toxicity to epithelial cells.