Wang Gensheng, Fowler Bruce A
Department of Experimental Radiation Oncology, U.T.M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Toxicol Appl Pharmacol. 2008 Nov 15;233(1):92-9. doi: 10.1016/j.taap.2008.01.017. Epub 2008 Jan 31.
Human exposure to environmental chemicals is most correctly characterized as exposure to mixtures of these agents. The metals/metalloids, lead (Pb), cadmium (Cd), and arsenic (As), are among the leading toxic agents detected in the environment. Exposure to these elements, particularly at chronic low dose levels, is still a major public health concern. Concurrent exposure to Pb, Cd, or As may produce additive or synergistic interactions or even new effects that are not seen in single component exposures. Evaluating these interactions on a mechanistic basis is essential for risk assessment and management of metal/metalloid mixtures. This paper will review a number of individual studies that addressed interactions of these metals/metalloids in both experimental and human exposure studies with particular emphasis on biomarkers. In general, co-exposure to metal/metalloid mixtures produced more severe effects at both relatively high dose and low dose levels in a biomarker-specific manner. These effects were found to be mediated by dose, duration of exposure and genetic factors. While traditional endpoints, such as morphological changes and biochemical parameters for target organ toxicity, were effective measures for evaluating the toxicity of high dose metal/metalloid mixtures, biomarkers for oxidative stress, altered heme biosynthesis parameters, and stress proteins showed clear responses in evaluating toxicity of low dose metal/metalloid mixtures. Metallothionein, heat shock proteins, and glutathione are involved in regulating interactive effects of metal/metalloid mixtures at low dose levels. These findings suggest that further studies on interactions of these metal/metalloid mixtures utilizing biomarker endpoints are highly warranted.
人类接触环境化学物质最确切的特征是接触这些物质的混合物。金属/类金属，如铅（Pb）、镉（Cd）和砷（As），是环境中检测到的主要有毒物质。接触这些元素，尤其是长期低剂量接触，仍然是一个主要的公共卫生问题。同时接触铅、镉或砷可能会产生相加或协同相互作用，甚至产生单一成分接触中未出现的新效应。从机制角度评估这些相互作用对于金属/类金属混合物的风险评估和管理至关重要。本文将综述一些针对这些金属/类金属在实验和人体接触研究中的相互作用的单项研究，特别强调生物标志物。一般来说，同时接触金属/类金属混合物在相对高剂量和低剂量水平上均以生物标志物特异性方式产生更严重的影响。发现这些影响由剂量、接触持续时间和遗传因素介导。虽然传统终点，如形态学变化和靶器官毒性的生化参数，是评估高剂量金属/类金属混合物毒性的有效指标，但氧化应激生物标志物、血红素生物合成参数改变和应激蛋白在评估低剂量金属/类金属混合物毒性时显示出明显反应。金属硫蛋白、热休克蛋白和谷胱甘肽参与调节低剂量水平下金属/类金属混合物的相互作用。这些发现表明，利用生物标志物终点对这些金属/类金属混合物的相互作用进行进一步研究非常必要。
