Biotic and Abiotic Transformation of Organo-Arsenic Compounds
Exposure to high levels of organic arsenic compounds can come from seafood consumption. While arsenobetaine, the most prevalent form of arsenic in fish, is non-toxic and not metabolized by humans, significant amounts of other organic arsenic compounds, including arsenosugars and arsenolipids, can also be present in seafood. Both arsenosugars and arsenolipids are broken down during metabolism, and one of their metabolites (thio-dimethyl arsenic), as well as some arsenolipid compounds (arsenic-containing hydrocarbons) have been found to be toxic in cell assays, demonstrating an urgent need to better understand the exposure and effects of these compounds. In this pilot project, we are laying the framework for characterizing and quantifying these compounds, and using innovative in vitro cell assay techniques to examine their rate of uptake and metabolic pathway, and their effects on immune cells.
Fate of Androscoggin River Floodplain Mercury from the Chlor-Alkali Facility Superfund Site, Berlin, NH
The former Chlor-Alkali Facility in Berlin, New Hampshire was listed on the National Priorities (Superfund) list in 2005 for its mercury discharges into the Androscoggin River. Despite remediation efforts, there are still high levels of mercury in the river floodplain and while floodplains are generally effective at absorbing and storing chemicals, certain natural processes can release mercury stored in the soil. For example, soil saturation through rainfall changes the soil conditions, allowing mercury in the soil to be converted into forms that can move freely through the environment. Climate predictions for New Hampshire suggest an increase in regional rainfall that could promote mercury conversion, releasing mercury stored in the soil to enter river and downstream surface waters. In our pilot study, we are examining the interactions between the floodplain’s seasonal patterns and the organisms and chemicals in its soils to understand how mercury is converted to its more mobile form and assess the likelihood of mercury releases into the river channel and atmosphere in the future.
Effects of Arsenic Ingestion on Antiviral T Cell Responses
This pilot study will build on an interesting set of observations in murine influenza, after treatment with 100 ppb Arsenic (As) in their drinking water, which showed that As-treated infected animals have a delay in influenza virus clearance compared to untreated infected mice. Of particular interest, the T cell responses in the lung were significantly delayed, though considerably more robust infiltration than in the lungs of untreated mice. Though the exploratory data suggested a defect in antigen presentation by dendritic cells, there have been no explorations into the functions and activities of the antiviral T cells (essential for clearance), the degree to which their effector activities were either impaired (allowing prolonged viral clearance) or dysregulated (resulting in greater injury to the airways). This pilot study is designed to test the hypothesis that ingestion of 100 ppb arsenic prior to infection impairs the activation and expansion of CD8+ T cells in response to influenza infection, as well as the hypothesis that ingestion of 100 ppb arsenic prior to infection impairs the downregulation and contraction of CD8+ T cells during clearance of influenza infection. We have previously shown that the magnitude of the inflammatory infiltration, while delayed, is greater in As-treated versus untreated controls after sub-lethal influenza infection. We want to characterize the programmed expression of pro-apoptotic mediators expressed by antiviral T cells upon activation.