GROWTH CONTROL IN EPITHELIAL CELLS AND ITS ALTERATION IN CARCINOGENESIS

进一步鉴定了胎鼠肺上皮细胞系(FRLE) 其肺泡II型起源并用于肿瘤研究 细胞因子和基因的转化及其分子机制 表情。FRLE细胞，脂质体pZipyK12yCys(携带 K-ras癌基因在密码子12上有Gly到Cys突变)导致11 转化的细胞系，在裸鼠和裸鼠体内具有高致瘤性。 FRLE胞质内弥漫着板层体样细胞器 在转化的细胞系中聚集的细胞，固体中不存在 裸鼠体内的肿瘤，但在继代培养的细胞中再次出现 肿瘤，表明肿瘤性转化并未取消特定的 分化的标志物。板层小体的存在与 与PAN-ras p21蛋白表达有关。对黄曲霉毒素的影响研究 FRLE细胞上的晶态二氧化硅表现出明显的剂量依赖性 石英的毒性和锐钛矿(一种非致纤维化钛)的低毒 二氧化碳)。抗氧化剂2-PVPNO[聚(2-乙烯基吡啶-N-氧化物)]和 4-PVPNO可抑制石英对该细胞的细胞毒作用。 建立了肿瘤转化的初步方法。 FRLE细胞由结晶性二氧化硅和其他致癌物引起。酶联免疫吸附试验 显示未经处理的FRLE细胞分泌转化生长因子 β-1(转化生长因子-β1)，并促进细胞分泌转化生长因子-β1。 肿瘤变形者。证实了转化生长因子-β1前体 FRLE细胞癌变的免疫组织化学研究石英砂 被发现通过以下方式诱导转化生长因子-β1的分泌显著增加 2-PVPNO还可诱导转化生长因子-β1的分泌增加； 石英和PVPNO的联合处理，尽管毒性较低， 进一步增加转化生长因子-β1的分泌。在未经处理的FRLE细胞中， 转化生长因子-β1的分泌与细胞呈线性关系。 密度，暗示了一种自动诱导机制。

The fetal rat lung epithelial cell line (FRLE) was further characterized for its alveolar type II origin and used for studies on neoplastic transformation and on molecular mechanisms of cytokines and gene expression. FRLE cells, lipofected with plasmid pZipyK12yCys (carrying a K-ras oncogene with a Gly to Cys mutation on codon 12) resulted in 11 transformed cell lines, highly tumorigenic in nude mice and nude rats. Lamellar body-like organelles were disseminated in the cytoplasm of FRLE cells, aggregated in the transformed cell lines, absent in the solid tumors in nude mice, but present again in cells subcultured from the tumors, showing that neoplastic transformation had not abolished specific markers of differentiation. Presence of lamellar bodies was correlated with the expression of pan-ras p21 protein. Studies on the effects of crystalline silica on the FRLE cells showed marked dose-dependent toxicity of quartz and low toxicity of anatase (a non-fibrogenic titanium dioxide). The antioxidants, 2-PVPNO [poly(2-vinyl-pyridine-N-oxide)] and 4-PVPNO, were shown to inhibit quartz cytotoxicity in this cell line. Preliminary methods were developed for the neoplastic transformation of FRLE cells by crystalline silica and other carcinogens. ELISA assays showed that untreated FRLE cells secreted transforming growth factor beta1 (TGF-beta1), and the secretion of TGF-beta1 was increased in their neoplastic transformants. TGF-beta1 precursor was demonstrated immunohistochemically in neoplastic transformants of FRLE cells. Quartz was found to induce a marked increase in the secretion of TGF-beta1 by FRLE cells; 2-PVPNO also induced increased secretion of TGF-beta1; combined treatment with quartz and PVPNO, in spite of lowered toxicity, further increased the secretion of TGF-beta1. In untreated FRLE cells, secretion of TGF-beta1 was found to be linearly dependent on cell density, suggesting an autoinduction mechanism.