Molecular and Environmental Science Research Group, Department of Geological Sciences, University of Saskatchewan, Saskatoon, SK, Canada.
ACS Chem Biol. 2012 Feb 17;7(2):411-20. doi: 10.1021/cb200287c. Epub 2011 Nov 7.
Mercury, one of the most toxic elements, exists in various chemical forms each with different toxicities and health implications. Some methylated mercury forms, one of which exists in fish and other seafood products, pose a potential threat, especially during embryonic and early postnatal development. Despite global concerns, little is known about the mechanisms underlying transport and toxicity of different mercury species. To investigate the impact of different mercury chemical forms on vertebrate development, we have successfully combined the zebrafish, a well-established developmental biology model system, with synchrotron-based X-ray fluorescence imaging. Our work revealed substantial differences in tissue-specific accumulation patterns of mercury in zebrafish larvae exposed to four different mercury formulations in water. Methylmercury species not only resulted in overall higher mercury burdens but also targeted different cells and tissues than their inorganic counterparts, thus revealing a significant role of speciation in cellular and molecular targeting and mercury sequestration. For methylmercury species, the highest mercury concentrations were in the eye lens epithelial cells, independent of the formulation ligand (chloride versusl-cysteine). For inorganic mercury species, in absence of l-cysteine, the olfactory epithelium and kidney accumulated the greatest amounts of mercury. However, with l-cysteine present in the treatment solution, mercuric bis-l-cysteineate species dominated the treatment, significantly decreasing uptake. Our results clearly demonstrate that the common differentiation between organic and inorganic mercury is not sufficient to determine the toxicity of various mercury species.
汞是毒性最大的元素之一,存在多种化学形态,每种形态的毒性和对健康的影响都不同。一些甲基汞形态存在于鱼类和其他海鲜产品中,构成潜在威胁,尤其是在胚胎期和出生后早期。尽管全球对此表示关注,但对于不同汞形态的运输和毒性机制仍知之甚少。为了研究不同汞化学形态对脊椎动物发育的影响,我们成功地将斑马鱼(一种成熟的发育生物学模型系统)与基于同步加速器的 X 射线荧光成像技术相结合。我们的工作揭示了在水中暴露于四种不同汞制剂的斑马鱼幼虫中,汞在组织特异性积累模式方面存在显著差异。甲基汞形态不仅导致整体汞负荷更高,而且与无机形态相比,其靶向的细胞和组织也不同,从而揭示了形态在细胞和分子靶向以及汞螯合中的重要作用。对于甲基汞形态,无论制剂配体(氯化物与 l-半胱氨酸)如何,汞的最高浓度都存在于眼睛晶状体上皮细胞中。对于无机汞形态,在没有 l-半胱氨酸的情况下,嗅上皮和肾脏积累的汞最多。然而,在处理溶液中存在 l-半胱氨酸时,二巯基乙酸合汞物种占主导地位,显著减少了吸收。我们的研究结果清楚地表明,常见的有机汞和无机汞的区分不足以确定各种汞形态的毒性。