NEOPLASTIC TRANSFORMATION BY CRYSTALLINE SILICA AND OTHER MINERALS

胎儿体内石英颗粒诱发肿瘤转化 大鼠肺泡上皮细胞系，胎鼠肺上皮细胞（FRLE）， 在无血清MEM培养基中处理24小时，然后用MEM/10% 胎牛血清 三个实验表明，石英的诱导 上皮细胞形态改变的集落或病灶。 这些是 在裸鼠中传代培养和接种，其中它们引起 癌 最初的形态学突变产生了菌落， 软琼脂在裸鼠中也是致瘤的。 传代细胞 从裸鼠的肿瘤中提取的DNA也具有致瘤性。 肿瘤性 单次暴露于石英粉尘， 范围为12.5至100微克/平方厘米。 这一新颖的发现表明， 石英可诱发大鼠肺泡癌的发生 上皮细胞，提供了证据表明，石英颗粒可以转化为 直接靶向上皮细胞，而无需间充质细胞介导。 来自源自石英转化细胞的裸鼠肿瘤的细胞（QTT-2000）。 T1 C）的生长受到TGF-β 1和TGF-β 2的抑制， FRLE细胞，而来自裸鼠肿瘤的细胞来源于FRLE细胞 经突变ras质粒（RT-T1）转化的细胞相对不受影响。 TGF-β 1和TGF-β 2 mRNA在QTT-T1 C中表达水平较高 FRLE和RT-T1 C细胞中。 裸鼠来源的癌 从QTT和RT细胞不表达TGF-β潜伏相关的 蛋白质，类似于由石英诱导的大鼠癌，表明 转录后调节。 烟草特有的亚硝胺NNK 发现在FRLE细胞中诱导显著的剂量依赖性细胞毒性， 这表明FRLE细胞可以代谢活化NNK， 因此适合于石英和NNK的联合作用的研究。 伴生矿物在毒性和转化活性中的作用 通过使用BALB/3 T3/A31-1-1细胞的新结果证实了石英的存在 线 赤铁矿和赤铁矿是无毒和非转化的， 抑制毒性和转化石英。 金红石， 比石英毒性更大，但不转化，增强了石英的毒性， 而不是其转化活性。

Neoplastic transformation was induced by quartz particles in the fetal rat lung alveolar epithelial cell line, fetal rat lung epithelial (FRLE), treated in serum-free MEM medium for 24 hr and then fed with MEM/10% fetal bovine serum. Three experiments showed the induction by quartz of morphologically altered colonies or foci of epithelial cells. These were subcultured and inoculated in nude mice, in which they gave rise to carcinomas. The original morphological transformant yielded colonies in soft agar that were also tumorigenic in nude mice. Cells subcultured from the tumors in nude mice were, in turn, also tumorigenic. Neoplastic transformation was obtained with single exposures to quartz dust at doses ranging from 12.5 to 100 microg/cm2. This novel finding, showing that quartz can induce neoplastic transformation in rat lung alveolar epithelial cells, provides evidence that quartz particles can transform target epithelial cells directly, without mediation by mesenchymal cells. Cells from nude mouse tumors derived from quartz-transformed cells (QTT- T1C) were growth-inhibited by TGF-beta1 and TGF-beta2, as were the parent FRLE cells, whereas cells from nude mouse tumors derived from FRLE cells transformed by a mutated ras plasmid (RT-T1) were relatively unaffected. TGF-beta1 and TGF-beta2 mRNAs were expressed at higher levels in QTT-T1C cells than in FRLE and RT-T1C cells. Carcinomas in nude mice derived from QTT and RT cells did not express TGF-beta latency-associated protein, in analogy with carcinomas induced in rats by quartz, suggesting a posttranscriptional regulation. The tobacco-specific nitrosamine, NNK, was found to induce marked dose-dependent cytotoxicity in FRLE cells, indicating that FRLE cells can metabolically activate NNK and are therefore appropriate for studies on combined effects of quartz and NNK. The role of associated minerals on the toxicity and transforming activity of quartz was confirmed by new results using the BALB/3T3/A31-1-1 cell line. Hematite and anatase were nontoxic and nontransforming and inhibited both toxicity and transformation by quartz. Rutile, which was more toxic than quartz, but nontransforming, enhanced quartz toxicity, but not its transforming activity.