Holmes Amie L, Wise Sandra S, Sandwick Sarah J, Wise John Pierce
Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, 96 Falmouth Street, Portland, ME 04104-9300, United States.
Mutat Res. 2006 Nov 7;610(1-2):8-13. doi: 10.1016/j.mrgentox.2006.06.006. Epub 2006 Jul 25.
Hexavalent chromium (Cr(VI)) is a well-designated human lung carcinogen, with solubility playing an important role in its carcinogenic potential. Although it is known that particulate or water-insoluble Cr(VI) compounds are more potent than the soluble species of this metal, the mechanisms of action are not fully elucidated. In this study, we investigated the hypothesis that the difference in potency between particulate and soluble Cr(VI) is due to more chronic exposures with particulate chromate because it can deposit and persist in the lungs while soluble chromate is rapidly cleared. Chronic exposure to both insoluble lead chromate and soluble sodium chromate induced a concentration and time-dependent increase in intracellular Cr ion concentrations in cultured human lung fibroblasts. Intracellular Pb levels after chronic exposure to lead chromate increased in a concentration-dependent manner but did not increase with longer exposure times up to 72 h. We also investigated the effects of chronic exposure to Cr(VI) on clastogenicity and found that chronic exposure to lead chromate induces persistent or increasing chromosome damage. Specifically, exposure to 0.5 microg/cm(2) lead chromate for 24, 48 and 72 h induced 23, 23 and 27% damaged metaphases, respectively. Contrary to lead chromate, the amount of chromosome damage after chronic exposure to sodium chromate decreased with time. For example, cells exposed to 1 microM sodium chromate for 24, 48 and 72 h induced 23, 13 and 17% damaged metaphases, respectively. Our data suggest a possible mechanism for the observed potency difference between soluble and insoluble Cr(VI) compounds is that chronic exposure to particulate Cr(VI) induces persistent chromosome damage and chromosome instability while chromosome damage is repaired with chronic exposure to soluble Cr(VI).
六价铬（Cr(VI)）是一种公认的人类肺癌致癌物，其溶解性在致癌潜力方面起着重要作用。尽管已知颗粒状或水不溶性Cr(VI)化合物比该金属的可溶性物种更具致癌性，但其作用机制尚未完全阐明。在本研究中，我们探讨了一个假设，即颗粒状和可溶性Cr(VI)之间致癌性差异的原因是颗粒状铬酸盐的暴露时间更长，因为它可以沉积并持续存在于肺部，而可溶性铬酸盐会迅速清除。长期暴露于不溶性铬酸铅和可溶性铬酸钠均会导致培养的人肺成纤维细胞内Cr离子浓度呈浓度和时间依赖性增加。长期暴露于铬酸铅后，细胞内铅水平呈浓度依赖性增加，但在长达72小时的较长暴露时间内并未增加。我们还研究了长期暴露于Cr(VI)对染色体断裂的影响，发现长期暴露于铬酸铅会导致持续性或增加的染色体损伤。具体而言，暴露于0.5微克/平方厘米的铬酸铅24、48和72小时分别诱导了23%、23%和27%的中期细胞受损。与铬酸铅相反，长期暴露于铬酸钠后染色体损伤的数量随时间减少。例如，暴露于1微摩尔/升铬酸钠24、48和72小时的细胞分别诱导了23%、13%和17%的中期细胞受损。我们的数据表明，可溶性和不溶性Cr(VI)化合物之间观察到的致癌性差异的一种可能机制是，长期暴露于颗粒状Cr(VI)会导致持续性染色体损伤和染色体不稳定，而长期暴露于可溶性Cr(VI)时染色体损伤会得到修复。
