Huang X, Fournier J, Koenig K, Chen L C
Department of Environmental Medicine, New York University Medical Center, 550 First Avenue, New York, New York 10016, USA.
Chem Res Toxicol. 1998 Jul;11(7):722-9. doi: 10.1021/tx970151o.
Epidemiological studies have shown that the prevalence of coal workers' pneumoconiosis (CWP) differed remarkably between different coal mine regions despite comparable exposures to respirable dust. In the United States, CWP was found to be most common in Pennsylvania coal miners and least common in miners from Utah. The active component(s) responsible for the regional differences in CWP has not yet been identified. In the present study, we found that coals from Pennsylvania, compared with Utah coals, showed a much lower buffering capacity as determined by the amount of acid consumed in order to reach pH 4.5, which is the pH of the phagolysosomes of macrophages. Moreover, the coals from Pennsylvania released large amounts of Fe2+ in the acidified extract, whereas the coals from Utah released little Fe2+. Using electron spin resonance (ESR), we found that the coals from Pennsylvania, but not from Utah, were effective in oxidizing formate by a radical pathway. Two coals, one from Utah with high buffering capacity and low acid-soluble Fe2+ and the other from Pennsylvania with low buffering capacity and high acid-soluble Fe2+, were then selected for cell treatment. We found that human tracheal epithelial (HTE) cells treated with the coal from Pennsylvania (10 microg/cm2) showed a 36% increase in oxidant formation over the control as detected by dichlorofluorescein assay, whereas the coal from Utah had no effect. An electrophoretic mobility shift assay was used to test the binding affinity of nuclear proteins extracted from the coal-treated HTE cells to an oxidative stress-responsive transcription factor activator protein-1 (AP-1) element. The coal from Pennsylvania with high acid-soluble Fe2+ (1 microg/cm2) activated AP-1 to the same extent as 10 microM H2O2, while the coal from Utah without acid-soluble Fe2+ had no effect. These results support our hypothesis that the prevalence of CWP may be higher in coal workers exposed to coal with high acid-soluble Fe2+ and low buffering capacity than in workers exposed to coal with low acid-soluble Fe2+ and high buffering capacity.
流行病学研究表明,尽管接触的可吸入粉尘量相当,但不同煤矿地区煤工尘肺(CWP)的患病率却有显著差异。在美国,发现CWP在宾夕法尼亚州的煤矿工人中最为常见,而在犹他州的矿工中最不常见。导致CWP地区差异的活性成分尚未确定。在本研究中,我们发现,与犹他州的煤相比,宾夕法尼亚州的煤表现出低得多的缓冲能力,这是通过达到pH 4.5(巨噬细胞吞噬溶酶体的pH值)所消耗的酸量来确定的。此外,宾夕法尼亚州的煤在酸化提取物中释放大量Fe2+,而犹他州的煤释放的Fe2+很少。使用电子自旋共振(ESR),我们发现宾夕法尼亚州的煤而非犹他州的煤能够通过自由基途径有效氧化甲酸盐。然后选择了两种煤,一种来自犹他州,具有高缓冲能力和低酸溶性Fe2+,另一种来自宾夕法尼亚州,具有低缓冲能力和高酸溶性Fe2+,用于细胞处理。我们发现,用来自宾夕法尼亚州的煤(10微克/平方厘米)处理的人气管上皮(HTE)细胞,通过二氯荧光素测定法检测,与对照相比,氧化剂形成增加了36%,而来自犹他州的煤则没有影响。使用电泳迁移率变动分析来测试从经煤处理的HTE细胞中提取的核蛋白与氧化应激反应转录因子激活蛋白-1(AP-1)元件的结合亲和力。具有高酸溶性Fe2+(1微克/平方厘米)的宾夕法尼亚州的煤激活AP-1的程度与10微摩尔/升H2O2相同,而没有酸溶性Fe2+的犹他州的煤则没有影响。这些结果支持了我们的假设,即与接触低酸溶性Fe2+和高缓冲能力煤的工人相比,接触高酸溶性Fe2+和低缓冲能力煤的煤矿工人中CWP的患病率可能更高。