Wise Sandra S, Holmes Amie L, Wise John Pierce
Wise Laboratory of Environmental and Genetic Toxicology, Maine Center for Toxicology and Environmental Health, University of Southern Maine, PO Box 9300, Portland, ME 04103-9300, United States.
Mutat Res. 2006 Nov 7;610(1-2):2-7. doi: 10.1016/j.mrgentox.2006.06.005. Epub 2006 Jul 26.
Particulate hexavalent chromium (Cr(VI)) is a well-established human lung carcinogen. It is currently a major public health concern, there is widespread exposure to it in occupational settings and to the general public. However, despite the potential widespread exposure and the fact that the lung is its target organ, few studies have considered the toxic effects of particulate Cr(VI) in human lung cells. Accordingly, we used lead chromate as a model particulate Cr(VI) compound and determined its cytotoxicity and genotoxicity in cultured human bronchial epithelial cells, using BEP2D cells as a model cell line. We found that lead chromate induced concentration-dependent cytotoxicity in BEP2D cells after a 24h exposure. Specifically, the relative survival was 78, 59, 53, 46 and 0% after exposure to 0.5, 1, 5, 10 and 50 microg/cm(2) lead chromate, respectively. Similarly, the amount of chromosome damage increased with concentration after 24h exposure to lead chromate. Specifically, 0.5, 1, 5 and 10 microg/cm(2) damaged 10, 13, 20 and 28% of metaphase cells with the total amount of damage reaching 11, 15, 24 and 36 aberrations per 100 metaphases, respectively. Lead chromate (50 microg/cm(2) lead chromate) induced profound cell cycle delay and no metaphases were found. In addition we investigated the effects of soluble hexavalent chromium, sodium chromate, in this cell line. We found that 1, 2.5, 5 and 10 microM sodium chromate induced 66, 35, 0 and 0% relative survival, respectively. The amount of chromosome damage increased with concentration after 24h exposure to sodium chromate. Specifically, 1, 2.5 and 5 microM damaged 25, 34 and 41% of metaphase cells with the total amount of damage reaching 33, 59 and 70 aberrations per 100 metaphases, respectively. Ten micromolar sodium chromate induced profound cell cycle delay and no metaphases were found. Overall the data clearly indicate that hexavalent Cr(VI) is cytotoxic and genotoxic to human lung epithelial cells.
颗粒态六价铬（Cr(VI)）是一种公认的人类肺癌致癌物。它目前是一个主要的公共卫生问题，在职业环境和普通公众中都存在广泛接触。然而，尽管存在潜在的广泛接触且肺部是其靶器官，但很少有研究考虑颗粒态Cr(VI)对人肺细胞的毒性作用。因此，我们使用铬酸铅作为颗粒态Cr(VI)化合物的模型，并以BEP2D细胞作为模型细胞系，测定其在培养的人支气管上皮细胞中的细胞毒性和遗传毒性。我们发现，铬酸铅在24小时暴露后对BEP2D细胞诱导了浓度依赖性的细胞毒性。具体而言，暴露于0.5、1、5、10和50微克/平方厘米铬酸铅后，相对存活率分别为78%、59%、53%、46%和0%。同样，在24小时暴露于铬酸铅后，染色体损伤数量随浓度增加。具体而言，0.5、1、5和10微克/平方厘米分别使10%、13%、20%和28%的中期细胞受损，每100个中期细胞的总损伤量分别达到11、15、24和36个畸变。铬酸铅（50微克/平方厘米铬酸铅）诱导了严重的细胞周期延迟，未发现中期细胞。此外，我们研究了可溶性六价铬铬酸钠在该细胞系中的作用。我们发现，1、2.5、5和10微摩尔铬酸钠分别诱导了66%、35%、0%和0%的相对存活率。在24小时暴露于铬酸钠后，染色体损伤数量随浓度增加。具体而言，1、2.5和5微摩尔分别使25%、34%和41%的中期细胞受损，每100个中期细胞的总损伤量分别达到33、59和70个畸变。10微摩尔铬酸钠诱导了严重的细胞周期延迟，未发现中期细胞。总体而言，数据清楚地表明六价Cr(VI)对人肺上皮细胞具有细胞毒性和遗传毒性。
