RESPIRATORY CARCINOGENESIS BY CHEMICAL AND PHYSICAL FACTORS

尘肺患者肺组织学研究 和/或肺癌显示了几例肺泡II型增生 邻近纤维化病变和邻近双折射沉积物 灰尘颗粒 这一新的观察表明， 矽肺大鼠模型中的癌前上皮反应- 相关的肺癌。 TGF-β免疫组织化学定位 β 1前体，在体内滴注石英后，显示 大鼠（对二氧化硅诱导的肺敏感）之间的显著差异 致癌作用）和两种耐药物种，小鼠和仓鼠。 在大鼠中， TGF-β 1前体早在10天就被检测到， 在增生的肺泡II型细胞中显著表达。 TGF-β 1的产生在小鼠中是最小的，在仓鼠中检测不到。 p21 ras蛋白的免疫组化定位为： 在二氧化硅的增生肺泡II型细胞中进一步证实， 治疗大鼠肺，但不是在腺瘤和癌。 因此，TGF- β 1前体和ras p21蛋白在增生性 肺泡II型细胞和两者在癌中下调，而在 只有p21 ras蛋白在存在 TGF-β 1前体;这些被提议作为诊断标志物。 二氧化硅 电镜观察肺泡Ⅱ型细胞内有颗粒 在大鼠中支气管内滴注之后，通过显微镜（EM）观察。 的作用 结晶二氧化硅在纤维形成中的作用及其对上皮细胞的影响 在裸小鼠皮下注射石英后， 小鼠 弥漫性肝矽肉芽肿与桥接有关 坏死、窦内和门静脉纤维化和再生结节 在3个月和6个月。 到1年时，大融合性肉芽肿和严重 纤维化（肝硬化）破坏了肝脏结构。 二氧化硅颗粒 电镜显示，在肥大的库普弗细胞和脂肪储存 伊藤细胞 观察小鼠是否可能出现肝脏 癌 这是第一个证据表明，二氧化硅是纤维化， 在裸鼠肝脏中的致瘤性。 该模型用于细胞因子和 二氧化硅诱导的间充质上皮细胞中的基因表达研究 交互.

Histological studies of human lungs from subjects with pneumoconioses and/or lung cancer revealed several cases of alveolar type II hyperplasia adjacent to fibrotic lesions and in proximity to deposits of birefringent dust particles. This novel observation suggests an analogy with the preneoplastic epithelial reactions in the rat model of silicosis- associated lung carcinogenesis. Immunohistochemical localization of TGF- beta1 precursor, after intratracheal instillation of quartz, showed significant differences between rats (susceptible to silica-induced lung carcinogenesis) and two resistant species, mice and hamsters. In rats, TGF-beta1 precursor was detected as early as 10 days and it progressed to a marked level of expression in hyperplastic alveolar type II cells. TGF-beta1 production was minimal in mice and not detectable in hamsters. Immunohistochemical localization of pan-reactive p21 ras protein was further demonstrated in hyperplastic alveolar type II cells of silica- treated rat lungs, but not in adenomas and carcinomas. Thus, both TGF- beta1 precursor and ras p21 protein are expressed in hyperplastic alveolar type II cells and both downregulated in carcinomas, whereas in adenomas only p21 ras protein appears downregulated in the presence of TGF-beta1 precursor; these are proposed as diagnostic markers. Silica particles were demonstrated in alveolar type II cells by electron microscopy (EM), following intrabronchial instillation in rats. The role of crystalline silica in fibrogenesis and its effects on epithelial cells were studied in the liver after subcutaneous injection of quartz in nude mice. Diffuse hepatic silicotic granulomas were associated with bridging necrosis, intrasinusoidal and portal fibrosis and regenerative nodules at 3 and 6 months. By 1 year, large confluent granulomas and severe fibrosis (cirrhosis) disrupted the liver architecture. Silica particles were demonstrated by EM in hypertrophied Kupffer cells and fat-storing Ito cells. Mice are observed for possible development of liver carcinomas. This is the first evidence that silica is fibrogenic and cirrhogenic in the nude mouse liver. This model is used for cytokine and gene expression studies in silica-induced mesenchymal-epithelial interactions.