Cullen R T, Miller B G, Davis J M, Brown D M, Donaldson K
Institute of Occupational Medicine, Edinburgh, United Kingdom.
Environ Health Perspect. 1997 Sep;105 Suppl 5(Suppl 5):1235-40. doi: 10.1289/ehp.97105s51235.
A wide range of fiber types was tested in two in vitro assays: toxicity to A549 epithelial cells, as detachment from substrate, and the production of the proinflammatory cytokine tumor necrosis factor (TNF) by rat alveolar macrophages. Three of the fibers were also studied in vivo, using short-term inhalation followed by a) bronchoalveolar lavage to assess the inflammatory response and b) measurement of cell proliferation in terminal bronchioles and alveolar ducts, using incorporation of bromodeoxyuridine (BrdU). The amount of TNF produced by macrophages in vitro depended on the fiber type, with the man-made vitreous fibers, and refractory ceramic fibers being least stimulatory and silicon carbide (SiC) whiskers providing the greatest stimulation. In the epithelial detachment assay there were dose-dependent differences in the toxicity of the various fibers, with long amosite being the most toxic. However, there was no clear relationship to known chronic pathogenicity. Fibers studied by short-term inhalation produced some inflammation, but there was no clear discrimination between the responses to code 100/475 glass fibers and the more pathogenic amosite and SiC. However, measurements of BrdU uptake into lung cells showed that amosite and SiC produced a greater reaction than code 100/475, which itself caused no more proliferation than that seen in untreated lungs. These results mirror the pathogenicity ranking of the fibers in long-term experiments. In conclusion, the only test to show potential as a predictive measure of pathogenicity was that of cell proliferation in lungs after brief inhalation exposure (BrdU assay). We believe that this assay should be validated with a wider range of fibers, doses, and time points.
对A549上皮细胞的毒性（以从基质上脱离为指标），以及大鼠肺泡巨噬细胞促炎细胞因子肿瘤坏死因子（TNF）的产生。还对其中三种纤维进行了体内研究，采用短期吸入，随后进行：a）支气管肺泡灌洗以评估炎症反应，b）使用溴脱氧尿苷（BrdU）掺入法测量终末细支气管和肺泡管中的细胞增殖。巨噬细胞在体外产生的TNF量取决于纤维类型，人造玻璃纤维和难熔陶瓷纤维的刺激作用最小，而碳化硅（SiC）晶须的刺激作用最大。在上皮细胞脱离试验中，各种纤维的毒性存在剂量依赖性差异，长直闪石的毒性最大。然而，与已知的慢性致病性没有明确关系。通过短期吸入研究的纤维产生了一些炎症，但对100/475号玻璃纤维与致病性更强的直闪石和SiC的反应之间没有明显区分。然而，对肺细胞中BrdU摄取的测量表明，直闪石和SiC产生的反应比100/475号玻璃纤维更大，而100/475号玻璃纤维本身引起的增殖并不比未处理的肺中观察到的更多。这些结果反映了纤维在长期实验中的致病性排名。总之，唯一显示出作为致病性预测指标潜力的试验是短暂吸入暴露后肺细胞增殖试验（BrdU试验）。我们认为，该试验应该用更广泛的纤维、剂量和时间点进行验证。
