TRANSFORMING GROWTH-FACTOR-BETA-1, RAS AND P53 IN SILICA-INDUCED FIBROGENESIS AND CARCINOGENESIS

The pathogenesis of mesenchymal and epithelial lung reactions was stud ied after a single intratracheal instillation of quartz into rats. Rel ationships between transforming growth factor beta 1 (TGF-beta 1) and the ras and p53 genes were investigated in silicosis and associated lu ng cancer. Immunohistochemical reactivity to mature TGF-beta 1 was loc alized intracellularly in fibroblasts and macrophages at the periphery of silicotic granulomas and in stroma adjacent to hyperplastic alveol ar type II cells and extracellularly in connective tissue matrix adjac ent to hyperplastic alveolar type II cells. TGF-beta 1 precursor was l ocalized intracellularly in hyperplastic alveolar type II cells adjace nt to granulomas and in the cells of adenomas, but not in carcinomas. Hematite-treated controls showed no reactivity to TGF-beta 1. Immunohi stochemical localization of pan-reactive p21 ras protein in quartz-tre ated rat lunes was increased in hyperplastic alveolar type II cells ad jacent to granulomas, but not in adenomas and carcinomas. Foci of nucl ear immunoreactivity to p53 protein were observed in 25% of the carcin omas.