Williams A O, Saffiotti U
Laboratory of Experimental Pathology, National Cancer Institute, Bethesda, Maryland 20892-0041, USA.
Scand J Work Environ Health. 1995;21 Suppl 2:30-4.
The pathogenesis of mesenchymal and epithelial lung reactions was studied after a single intratracheal instillation of quartz into rats. Relationships between transforming growth factor beta1 (TGF-beta1) and the ras and p53 genes were investigated in silicosis and associated lung cancer. Immunohistochemical reactivity to mature TGF-beta1 was localized intracellularly in fibroblasts and macrophages at the periphery of silicotic granulomas and in stroma adjacent to hyperplastic alveolar type II cells and extracellularly in connective tissue matrix adjacent to hyperplastic alveolar type II cells. TGF-beta1 precursor was localized intracellularly in hyperplastic alveolar type II cells adjacent to granulomas and in the cells of adenomas, but not in carcinomas. Hematite-treated controls showed no reactivity to TGF-beta1. Immunohistochemical localization of pan-reactive p21 ras protein in quartz-treated rat lungs was increased in hyperplastic alveolar type II cells adjacent to granulomas, but not in adenomas and carcinomas. Foci of nuclear immunoreactivity to p53 protein were observed in 25% of the carcinomas.
在大鼠经气管内单次注入石英后，对间充质和上皮性肺反应的发病机制进行了研究。在矽肺及相关肺癌中，研究了转化生长因子β1（TGF-β1）与ras和p53基因之间的关系。对成熟TGF-β1的免疫组织化学反应在矽肺肉芽肿周边的成纤维细胞和巨噬细胞内、增生的II型肺泡上皮细胞相邻的基质内呈细胞内定位，在增生的II型肺泡上皮细胞相邻的结缔组织基质中呈细胞外定位。TGF-β1前体在肉芽肿相邻的增生II型肺泡上皮细胞及腺瘤细胞内呈细胞内定位，但在癌细胞内未定位。经赤铁矿处理的对照组对TGF-β1无反应。在石英处理的大鼠肺中，与肉芽肿相邻的增生II型肺泡上皮细胞中泛反应性p21 ras蛋白的免疫组织化学定位增加，但在腺瘤和癌中未增加。在25%的癌中观察到p53蛋白的核免疫反应灶。
