Minimal uranium accumulation in lymphoid tissues following an oral 60-day uranyl acetate exposure in male and female C57BL/6J mice

Abstract

High levels of uranium (U) exist in soil, water, and air in the Southwestern United States due, in part, to waste generated from more than 160,000 abandoned hard rock mines located in this region. As a result, many people living in this region are chronically exposed to U at levels that have been linked to detrimental health outcomes. In an effort to establish a relevant in vivo mouse model for future U immunotoxicity studies, we evaluated the tissue distribution of U in immune organs; blood, bone marrow, spleen, and thymus, as well as femur bones, kidneys, and liver, following a 60-d drinking water exposure to uranyl acetate (UA) in male and female C57BL/6J mice. Following the 60-d exposure, there was low overall tissue retention of U (<0.01%) at both the 5 and the 50 ppm (mg/L) oral concentrations. In both male and female mice, there was limited U accumulation in immune organs. U only accumulated at low concentrations in the blood and bone marrow of male mice (0.6 and 16.8 ng/g, respectively). Consistent with previous reports, the predominant sites of U accumulation were the femur bones (350.1 and 399.0 ng/g, respectively) and kidneys (134.0 and 361.3 ng/g, respectively) of male and female mice. Findings from this study provide critical insights into the distribution and retention of U in lymphoid tissues following chronic drinking water exposure to U. This information will serve as a foundation for immunotoxicological assessments of U, alone and in combination with other metals.

Minimal uranium immunotoxicity following a 60-day drinking water exposure to uranyl acetate in male and female C57BL/6J mice

“…Results from this study show that drinking water exposure to U did not produce significant immunotoxicological alterations in male or female mice, likely resulting from limited U accumulation in immune organs (Bolt et al, 2018). We found subtle, albeit important sexspecific differences in U immunotoxicity in male and female mice.…”

“…In an effort to better understand the minimal immunotoxicity observed in this study, we also evaluated the distribution of U in immune tissues of male and female mice following a 60day drinking water exposure to 5 and 50 ppm U (Bolt et al, 2018). Not surprisingly, we found very little U accumulation in the spleen and thymus.…”

“…The goal of the current study was to evaluate the immunotoxicity of U in male and female mice following a 60-day drinking water exposure to environmentally relevant levels of U (Bolt et al, 2018), using a set of conventional immunotoxicity assays (Burchiel et al, 2009;Boverhof et al, 2014). To our knowledge, this is the first study to evaluate the immunotoxicity of U (in the form of UA) following a chronic drinking water exposure in both male and female mice.…”

“…Interestingly, we did observe a slight accumulation of U in the blood and bone marrow of male, but not female mice, which might explain the slight sex-specific differences observed. Bone and bone marrow were found to be sites of significant U accumulation (Bolt et al, 2018) and as a result, immune cell populations in the bone marrow will be a focus of our future immunotoxicological investigations.…”

Exposures to uranium and arsenic alter intraepithelial and innate immune cells in the small intestine of male and female mice

“…U and total As concentrations were measured using a PerkinElmer NexION 300D ICP-MS (Waltham, MA) in the upper and lower GI tract of male and female mice as previously described (Bolt et al, 2018). The upper and lower GI tract were weighed prior to acid digestion, which was performed using 70% trace metal grade nitric acid and by heating the samples to 95°C overnight.…”