Postdoctoral Fellow, University of New Mexico
Interactions between arsenic and uranium immunotoxicity
Arsenic and uranium are environmental metal contaminants, particular found in the southwest. Elevated levels of arsenic and uranium have been reported in the water and air in several Indian reservations in the southwest four corners. Exposure to arsenic and uranium is associated with increased prevalence of immune disorders, including autoimmune diseases. Arsenic has been shown to cause immunotoxicity in immature B and T cells. However very little is known of the potential immunotoxic effects of uranium. My project is investigating the potential immunotoxic effects of uranium and determining if there are any interactions between arsenic and uranium-induced immunotoxicity since these two metals tend to co-occur in the environment. This work will help to determine the potential risks of exposure to these metals and help to determine useful strategies to help protect people exposed in the environment.
Abstract: Environmental arsenic exposure is a public health issue. Immunotoxicity induced by arsenic has been reported in humans and animal models. The purpose of this study was to evaluate mechanisms of As(+3) and MMA(+3) toxicity in mouse thymus cells. Because we know that MMA(+3) inhibits IL-7 signaling in mouse bone marrow pre-B cells, we studied the influence of As(+3) and MMA(+3) on T cell development in the thymus at the earliest stage of T cell development (CD4-CD8-, double negative, DN) which requires IL-7 dependent signaling. We found in a DN thymus cell line (D1) that a low concentration of MMA(+3) (50nM) suppressed IL-7 dependent JAK1, 3 and STAT5 signaling. As(+3) suppressed STAT5 and JAK3 at higher concentrations (500nM). Cell surface expression of the IL-7 receptor (CD127) was also suppressed by 50nM MMA(+)3, but was increased by 500nMAs(+3), indicating possible differences in the mechanisms of action of these agents. A decrease in cyclin D1 protein expression was observed in D1 cells exposed to As(+3) at 500nM and MMA(+3) starting at 50nM, suggesting that arsenic at these environmentally-relevant doses suppresses early T cell development through the inhibition of IL-7 signaling pathway.
Pub.: 28 Feb '16, Pinned: 13 Sep '17
Abstract: It is known in humans and mouse models, that drinking water exposures to arsenite (As(+3)) leads to immunotoxicity. Previously, our group showed that certain types of immune cells are extremely sensitive to arsenic induced genotoxicity. In order to see if cells from different immune organs have differential sensitivities to As(+3), and if the sensitivities correlate with the intracellular concentrations of arsenic species, male C57BL/6J mice were dosed with 0, 100 and 500ppb As(+3) via drinking water for 30 d. Oxidation State Specific Hydride Generation- Cryotrapping- Inductively Coupled Plasma- Mass Spectrometry (HG- CT- ICP- MS) was applied to analyze the intracellular arsenic species and concentrations in bone marrow, spleen and thymus cells isolated from the exposed mice. A dose-dependent increase in intracellular monomethylarsonous acid (MMA(+3)) was observed in both bone marrow and thymus cells, but not spleen cells. The total arsenic and MMA(+3) levels were correlated with an increase in DNA damage in bone marrow and thymus cells. An in vitro treatment of 5, 50 and 500nM As(+3) and MMA(+3) revealed that bone marrow cells are most sensitive to As(+3) treatment, and MMA(+3) is more genotoxic than As(+3). These results suggest that the differential sensitivities of the three immune organs to As(+3) exposure are due to the different intracellular arsenic species and concentrations, and that MMA(+3) may play a critical role in immunotoxicity.
Pub.: 24 Sep '16, Pinned: 13 Sep '17
Abstract: Exposure to geogenic particulate matter (PM) comprised of mineral particles has been linked to human health effects. However, very little data exist on health effects associated with geogenic dust exposure in natural settings. Therefore, we characterized particulate matter size, metal chemistry, and health effects of dust collected from the Nellis Dunes Recreation Area (NDRA), a popular off-road vehicle area located near Las Vegas, NV. Adult female B6C3F1 mice were exposed to several concentrations of mineral dust collected from active and vegetated sand dunes in NDRA. Dust samples (median diameter: 4.4μm) were suspended in phosphate-buffered saline and delivered at concentrations ranging from 0.01 to 100mg dust/kg body weight by oropharyngeal aspiration. ICP-MS analyses of total dissolution of the dust resulted in aluminum (55,090μg/g), vanadium (70μg/g), chromium (33μg/g), manganese (511μg/g), iron (21,600μg/g), cobalt (9.4μg/g), copper (69μg/g), zinc (79μg/g), arsenic (62μg/g), strontium (620μg/g), cesium (13μg/g), lead 25μg/g) and uranium (4.7μg/g). Arsenic was present only as As(V). Mice received four exposures, once/week over 28-days to mimic a month of weekend exposures. Descriptive and functional assays to assess immunotoxicity and neurotoxicity were performed 24h after the final exposure. The primary observation was that 0.1 to 100mg/kg of this sand dune derived dust dose-responsively reduced antigen-specific IgM antibody responses, suggesting that dust from this area of NDRA may present a potential health risk.
Pub.: 09 Dec '15, Pinned: 13 Sep '17
Abstract: Regional water pollution and use of unregulated water sources can be an important mixed metals exposure pathway for rural populations located in areas with limited water infrastructure and an extensive mining history. Using censored data analysis and mapping techniques we analyzed the joint geospatial distribution of arsenic and uranium in unregulated water sources throughout the Navajo Nation, where over 500 abandoned uranium mine sites are located in the rural southwestern United States. Results indicated that arsenic and uranium concentrations exceeded national drinking water standards in 15.1 % (arsenic) and 12.8 % (uranium) of tested water sources. Unregulated sources in close proximity (i.e., within 6 km) to abandoned uranium mines yielded significantly higher concentrations of arsenic or uranium than more distant sources. The demonstrated regional trends for potential co-exposure to these chemicals have implications for public policy and future research. Specifically, to generate solutions that reduce human exposure to water pollution from unregulated sources in rural areas, the potential for co-exposure to arsenic and uranium requires expanded documentation and examination. Recommendations for prioritizing policy and research decisions related to the documentation of existing health exposures and risk reduction strategies are also provided.
Pub.: 23 Aug '16, Pinned: 13 Sep '17
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