Van Dyke Knox, Patel Shaily, Vallyathan Val
West Virginia Health Science Center, Department of Biochemistry and Molecular Pharmacology, Morgantown, WV 26506, USA.
J Biosci. 2003 Feb;28(1):115-9. doi: 10.1007/BF02970141.
A simple, fast, precise and biologically relevant toxicity assay for screening cytotoxicity of minerals would have distinct advantages due to its cost benefits and relative savings in time. Furthermore, a bioassay to differentiate acute and chronic in vivo pulmonary reactions could have potential value as predictors of fibrogenicity and pathogenicity. In this study we examined the potential use of lucigenin as a probe to evaluate the correlation between chemiluminescence (CL) generated by alveolar macrophages with the known cytotoxicity and patho genicity by conventional bioassays. In this study, we used small doses of dust (20 microg) to minimize cellular overload and to maintain homeostasis. Crystalline silica a highly fibrogenic dust was used as positive control and results are compared with those for bentonite, kaolin and talc. Among the three minerals compared with silica, bentonite was more reactive (27%) in CL assay and declined sharply compared to other minerals. This sudden decline in bentonite CL is caused by cytotoxicity leading to cell death. CL-induced by talc was comparable to silica and declines slowly. Kaolin on the other hand produced relatively a weaker (25%) CL compared to silica. Our data using relatively low doses of dust suggest that the CL assay may have a better predictive value in cytotoxicity evaluations compared to conventional toxicity assays.
一种用于筛选矿物质细胞毒性的简单、快速、精确且与生物学相关的毒性检测方法,因其成本效益和时间上的相对节省而具有明显优势。此外,一种能够区分急性和慢性体内肺部反应的生物检测方法,作为纤维化和致病性的预测指标可能具有潜在价值。在本研究中,我们研究了光泽精作为一种探针的潜在用途,以评估肺泡巨噬细胞产生的化学发光(CL)与通过传统生物检测方法测得的已知细胞毒性和致病性之间的相关性。在本研究中,我们使用小剂量粉尘(20微克)以尽量减少细胞过载并维持体内平衡。将高度致纤维化的结晶二氧化硅粉尘用作阳性对照,并将结果与膨润土、高岭土和滑石的结果进行比较。在与二氧化硅比较的三种矿物质中,膨润土在CL检测中反应性更强(27%),与其他矿物质相比急剧下降。膨润土CL的这种突然下降是由细胞毒性导致细胞死亡引起的。滑石诱导的CL与二氧化硅相当且下降缓慢。另一方面,高岭土产生的CL相对于二氧化硅较弱(25%)。我们使用相对低剂量粉尘的数据表明,与传统毒性检测相比,CL检测在细胞毒性评估中可能具有更好的预测价值。