Theses and Dissertations at Montana State University (MSU)
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Item Lymphocyte subpopulations and oxidative stress following sub-acute exposure to natural dust collected from the Nellis Dunes Recreational Area(Montana State University - Bozeman, College of Letters & Science, 2015) Leetham, Mallory Spencer; Chairperson, Graduate Committee: Deborah Keil; Deborah Keil and Jamie DeWitt were co-authors of the article, 'Oxidative stress and lung histopathology following sub-acute exposure to natural dust collected from the Nellis Dunes Recreation Area' submitted to the journal 'Bureau of Land Management Report' which is contained within this thesis.Exposure to particulate matter containing heavy metals has been linked to adverse health effects when exposure occurs in industrial settings; however, little data exist on effects associated with natural exposure settings. In this study, markers of oxidative stress and lymphocyte subpopulations in mice were observed following sub-acute exposure to metals-containing dust collected from a natural setting used heavily for off-road vehicle (ORV) recreation. Adult female B6C3F1 mice were exposed to concentrations of dust collected from seven types of surfaces at the Nellis Dunes Recreation Area. Dust representing each of the seven map units was prepared with a median diameter of < or = 4.5m and suspended in PBS immediately prior to oropharyngeal aspiration at concentrations from 0.01 - 100 mg of dust/kg body weight. Four exposures were given a week apart over 28-days to mimic a month of weekend exposures. Thymi, spleens and blood for evaluation of oxidative stress markers and lymphocyte sub-populations were collected 24 hours after the final exposure. Blood markers of oxidative stress included levels of free radicals, superoxide dismutase, total antioxidant capacity, and total glutathione. CD4, CD8, FoxP3, CD25, IL-17, and B220 cell surface markers were used for T and B cell identification using flow cytometry. Overall, no single surface type was able to consistently induce markers of oxidative stress at a particular dose or in a dose-responsive manner. The two highest concentrations of dust from one surface type increased two markers of oxidative stress, but results of other surface types were inconsistent. No statistically significant changes were observed in the splenic B220+ cells following NDRA dust exposure. Three CBN units (1, 2, and 6) showed decreases in splenic CD4+/CD25+/FoxP3- cells. These observations were relatively consistent with TiO 2, where a significant change at the highest exposure level was observed in only one measure of oxidative stress. Additionally, the TiO 2 dosing groups showed no significant changes in lymphocyte subpopulations. These results indicate that exposure to these natural, mineral dusts, under the exposure scenario of our study, while are unlikely to considerably increase the risk of oxidative damage systemically, may induce a reduction in some cell populations in exposed individuals.Item Exposure to a complex mixture of metals on geogenic dust : analysis of clinical chemistry, hematology, and epigenetic markers(Montana State University - Bozeman, College of Letters & Science, 2015) Murphy, Lacey Marie; Chairperson, Graduate Committee: Deborah KeilThe Nellis Dunes Recreational Area is a popular off road vehicle site in Clark County, Nevada comprised of dust containing high levels of naturally occurring heavy metals: aluminum, arsenic, cesium, chromium, cobalt, copper, iron, lead, magnesium, manganese, strontium, uranium, vanadium, and zinc. A human health risk assessment and toxicological study to estimate the risk for those who visit the area were conducted. Dust samples from throughout the area were collected and grouped into seven "combination units" (CBN) based on composition and emissivity. Clinical chemistry and hematological changes observed in mice from a sub-acute, dose-dependent, inhalation model were analyzed. Epigenetic markers, specifically 5-methylcytosine, were evaluated in genes known to regulate antibody production and secretion to elucidate a possible mode of action for antibody suppression observed in the murine model. Clinical chemistry and/or hematological changes were observed in each CBN unit, while no change was observed in 5-methylcytosine for PRDM1, PAX5, and XBP-1 transcription factor genes regulating the B-Cell to plasma cell differentiation pathway and antibody production. Exposing B6C3F1 mice to 100 mg/kg dust from NDRA did not have effects on the methylation of CpG islands located in promoter regions of PRDM1 or PAX5. Clinical chemistries and hematology varied with the differing characterizations of each CBN unit, though not all results were dose-responsive.