Profiling of Environmental Mixtures Containing Heavy Metals for Their Toxicity Pathways and Mechanism of Action

Authors

• M Ooka
• J Zhao
• L Zhang
• R Huang
• S Sakamuru
• J Hsieh
• B Collins
• J Dunnick
• D Dixon
• M Xia

Abstract

The soil, water, and air around heavy metal manufacturing facilities, processing plants, landfills, and mining sites are contaminated with a mixture of heavy metals. People living near contaminated U. S. Superfund Sites are constantly exposed to these heavy metals, and these exposures may potentially be related to adverse health outcomes. Although people are often exposed to several metals concurrently, the toxic effect of simultaneous exposure to multiple heavy metals has not been sufficiently evaluated. In this study, we assessed the toxicity of mixtures of metal compounds that are frequently detected at Superfund sites. We found that nickel/arsenic/cadmium and beryllium/arsenic/cadmium compound mixtures showed higher toxicity than their component compounds, indicating that the toxicity was potentiated in the mixture. To further study the mechanism behind the potentiated toxicity, we focused on the degree of oxidative stress since most toxic effects from heavy metals are related to oxidative stress. Cadmium mixtures were of particular concern with their ability to induce higher oxidative stress than their component compounds. The induced oxidative stress subsequently caused DNA damage, inhibited DNA synthesis, and activated p53. We also found that the mixtures induced secretion of interleukin 8 and angiogenesis more than their component compounds. The present study provides valuable information regarding heavy metal toxicity at U. S. Superfund sites.

Scientific Focus Area: Molecular Biology and Biochemistry

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