GROWTH CONTROL IN EPITHELIAL CELLS AND ITS ALTERATION IN CARCINOGENESIS

进一步鉴定胎鼠肺上皮细胞系（FRLE） 其肺泡II型起源，并用于肿瘤研究 细胞因子和基因的分子机制 表情 FRLE细胞，用质粒pZipyK 12 yCys（携带 一个K-ras癌基因，密码子12上有Gly到Cys突变）导致11例 转化的细胞系，在裸鼠和裸大鼠中高度致瘤性。 胞质内散在板层小体样细胞器 细胞，在转化细胞系中聚集，在固体中不存在 在裸鼠中的肿瘤，但再次出现在细胞继代培养从 肿瘤，表明肿瘤转化并没有消除特异性 分化标志物。 板层体的存在与 p21蛋白的表达。 影响的研究 结晶二氧化硅对FRLE细胞的作用表现出明显的剂量依赖性 石英的毒性和钛的低毒性 二氧化物）。 抗氧化剂2-PVPNO [聚（2-乙烯基-吡啶-N-氧化物）]和 4-PVPNO显示抑制该细胞系中的石英细胞毒性。 初步的方法被开发为肿瘤转化的 FRLE细胞受到结晶二氧化硅和其他致癌物质的影响。 ELISA测定 显示未处理的FRLE细胞分泌转化生长因子， TGF-β 1（TGF-β 1）的分泌增加， 肿瘤转化体。 TGF-β 1前体被证明 在FRLE细胞的肿瘤转化体中的化学计量。 石英 发现诱导TGF-β 1分泌的显著增加， FRLE细胞; 2-PVPNO也诱导TGF-β 1分泌增加; 用石英和PVPNO联合处理，尽管毒性降低， 进一步增加了TGF-β 1的分泌。 在未处理的FRLE细胞中， TGF-β 1的分泌被发现是线性依赖于细胞 密度，提示自诱导机制。

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.