QUANTITATIVE STUDIES ON CONCURRENT FACTORS IN NEOPLASTIC TRANSFORMATION

可呼吸尺寸的结晶二氧化硅样品(1-5微米 直径)对BALB/3T3/A31-1-1小鼠的影响 胚胎细胞系。使用了下列样品：(A)石英样品： MIN-U-SIL5(MQZ，美国标准制剂)，氢氟酸蚀刻 MQZ(HFMQZ，本实验室为去除杂质而准备的 DQ12和F600(两种标准 德国制剂)和标准制剂(中国的标准制剂)； (B)其他晶态二氧化硅：方石英和鳞石英(已制备 用于本实验室的合成粉尘)；和(C)用于 相比之下，通常是三氧化二铁。诱发肿瘤转化 由三个石英样品按以下活度顺序排列：MQZ、HFMQZ 和F600。转化的病灶中的细胞，都被发现为阳性 对裸鼠的致瘤性进行超低温保存，并用于核型分析 并用于激活癌基因表达的分子分析。 细胞毒性，由最初接触二氧化硅引起，表现为 菌落形成效率(CFE)降低，其次是储存 吞噬的颗粒，在存活的人中没有进一步的毒性迹象 细胞。目前的结果表明，负责 细胞毒性，以及可能的转化，发生在时间 颗粒与细胞膜相遇的间隔时间 并完成吞噬作用。关于毒物影响的假设 仅在此初始阶段发生，并通过处理 在选定的时间段内，使用不同的细胞生长抑制因子 毒性机制。降低高血压病患者血清浓度 培养基渐进性降低对照细胞的CFE 石英处理的细胞，后者总是显示出比例较低的 CFE高于对照细胞。细胞暴露于经下列条件调节的培养基中 与大剂量的二氧化硅孵育没有毒性，这表明 这种影响不是由于可溶性因素造成的。

Crystalline silica samples in the respirable size (1-5 microns in diameter) were studied for their effects in the BALB/3T3/A31-1-1 mouse embryo cell line. The following samples were used: (A) quartz samples: Min-U-Sil 5 (MQZ, a standard U.S. preparation), hydrofluoric-acid-etched MQZ (HFMQZ, prepared for this laboratory in order to remove impurities from the silica surface by HF-etching), DQ12 and F600 (two standard preparations from Germany) and CSQZ (a standard preparation from China); (B) other crystalline silica forms: cristobalite and tridymite (prepared synthetically for this laboratory); and (C) non-fibrogenic dusts for comparison, usually ferric oxide. Neoplastic transformation was induced by three samples of quartz in the following order of activity: MQZ, HFMQZ and F600. Cells from the transformed foci, all found to be positive for tumorigenicity in nude mice, were cryopreserved and used for karyotyping and for molecular analysis of activated oncogene expression. Cytotoxicity, induced by initial exposure to silica and expressed by decreased colony forming efficiency (CFE), was followed by storage of phagocytosed particles with no further signs of toxicity in the surviving cells. Current results suggest that the mechanisms responsible for cytotoxicity, and possibly for transformation, take place in the time interval between the encounter of the particles with the cell membrane and the completion of phagocytosis. The hypothesis that toxic effects occur only during this initial phase is being tested by treating the cells for selected periods of time with various inhibitors of the mechanisms of toxicity. Decreasing the serum concentrations in the medium progressively decreased the CFE of control cells and of quartz-treated cells, the latter always showing a proportionally lower CFE than control cells. Exposure of cells to media conditioned by incubation with large doses of silica showed no toxicity, suggesting that the effect is not due to soluble factors.