NEOPLASTIC TRANSFORMATION BY CRYSTALLINE SILICA AND OTHER MINERALS

对来自胎鼠肺的细胞的研究仍在继续 肺泡上皮细胞系FRLE，在其中有肿瘤性转化 可以直接由石英颗粒诱导，而不需要 间充质细胞。转化生长因子-βmRNAs和 在石英转化的细胞和衍生的肿瘤中有蛋白质的报道。 在裸鼠身上进行了额外的致瘤性测试 石英处理细胞和对照细胞。新的研究是按顺序进行的 研究石英在成熟期的诱导转变机制 肺泡上皮细胞来源于青壮年而非胎儿 老鼠的肺。由于大鼠肺泡II型细胞通常不能 它们在培养中保存了几代以上， 用含有永生基因的载体(SV40 T抗原或腺病毒2E1a)和/或选择性标记物。已转染 为上皮细胞的形态特征选择的菌落 形成路面状集落的多边形细胞被扩增并 第5代超低温保存。这些新的细胞系已经传代 至今已15次，并保持了正常的形态。 新细胞系的特性及石英诱导的细胞毒性研究 细胞毒性和转化正在进行中。转SV40Tag基因的细胞株 细胞系对石英诱导的毒性表现出更高的敏感性 转导E1a基因的细胞系。

Studies were continued on cells derived from the fetal rat lung alveolar epithelial cell line, FRLE, in which neoplastic transformation can be directly induced by quartz particles, without mediation by mesenchymal cells. The patterns of expression of TGF-beta mRNAs and proteins were reported in quartz-transformed cells and derived tumors. Additional tumorigenicity assays in nude mice were performed for quartz-treated and control cells. New studies were undertaken in order to investigate quartz-induced transformation mechanisms in mature alveolar epithelial cells derived from young adult rather than fetal rat lungs. Since rat alveolar type II cells usually cannot be maintained in culture for more than a few passages, they were transfected with plasmids containing immortalizing genes (either SV40 T antigen or adenovirus 2 E1A) and/or a selective marker. Transfected colonies, selected for morphological characteristics of epithelial polygonal cells forming pavement-like colonies, were expanded and cryopreserved at passage 5. These new cell lines have been passaged 15 times so far, and have maintained normal morphology. Characterization of the new cell lines and studies of quartz-induced cytotoxicity and transformation are under way. The SV40Tag-transfected cell line showed a much higher sensitivity to quartz-induced toxicity than the E1A-transfected cell line.