Medicine and Health Sciences Commons^™

Zinc Finger Dna Repair Protein Targets Of Arsenite In The Nucleotide Excision Repair Pathway, Juliana M. Huestis

Biomedical Sciences ETDs

Environmental arsenic exposure affects around 100 million people worldwide. Recent evidence shows that arsenite, even at low concentrations, may act as a co-carcinogen, by displacing zinc from the zinc finger motifs of certain DNA repair proteins, leaving them vulnerable to redox modification and loss of protein function. This study probes the physical chemistry underlying arsenite and zinc binding to XPA and PARP1, in the hope of illuminating some of the aspects of protein structure that determine susceptibility to arsenite binding. In this study, dissociation constants are determined for zinc and arsenite binding to peptides corresponding to the C4 zinc finger …

Mechanisms Of Arsenic-Induced Suppression Of Early Red Blood Cell Development, Sebastian Medina

Biomedical Sciences ETDs

Anemia adversely impacts the health of more than a billion people worldwide. A strong association between anemia and arsenic exposure has been reported in epidemiological studies from multiple countries. However, the mechanistic bases for the association between arsenic exposure and anemia is not fully understood. In this study, we found an inverse association between drinking water arsenic exposures and clinical indicators of anemia (i.e., red blood cell counts and hematocrit/packet cell volumes) in a cohort of men from rural Bangladesh enrolled in the Health Effects of Arsenic Longitudinal Study.

Follow-up studies in mice, revealed that 60-day exposure to trivalent inorganic …

Legacy Mining Metal Exposures Contribute To Circulating Oxidized Low Density Lipoprotein And Serum Inflammatory Potential In A Native Community, Molly Harmon

Biomedical Sciences ETDs

Numerous abandoned uranium mines (AUM) within the Navajo Nation contribute uranium (U), arsenic (As) and other metals to the soil, air and groundwater that continue to pose potential health risks to Navajo residents. The prevalence of inflammatory-related cardiovascular disease (CVD) and type 2 diabetes (T2D) has increased among the Navajo community in recent decades. Environmental exposure to metal contaminants may alter the circulation in ways that are associated with the inflammation-driven process of atherosclerotic plaque formation. Thus, we hypothesize that exposures to AUM metal contaminants are associated with pro-atherogenic changes in the circulation as evidenced by increased low-density lipoprotein (LDL) …

Mechanisms Of Low Dose Arsenic Lymphoid Stem Cell Immunotoxicity And Potential Interactions With Dibenzo[Def, P]Chrysene (Dbc), Peace Chinyere Ezeh

Biomedical Sciences ETDs

In vivo assessment of the effects of inorganic arsenic, arsenite (As+3), on the bone marrow (BM) immune progenitor cells in mice showed that 300 parts per billion (ppb) As+3 given over 30 days in drinking water, produced a decrease in total BM cells recovered and suppressed the lymphoid (pre-B) but not the myeloid (GM) progenitor cells colony forming units (CFUs). 75 and 300 ppb As+3 also suppressed spleen T-dependent antibody responses. There was no shift in the general markers of early hematopoietic stem cells, CD34 and CD38, or the mesenchymal stem cells, CD105, in the BM. Splenic CD45+ B cells …

Aberrant Neurogenic And Epigenetic Processes Are Associated With Depression Induced By Developmental Arsenic Exposure, Christina Rene Tyler

Biomedical Sciences ETDs

Arsenic is a pervasive environmental contaminant derived from both natural and anthropogenic sources. Epidemiological evidence supports a correlation between arsenic exposure in drinking water and increased rates of psychiatric disorders, including depression, in exposed populations. Previous studies have established that perinatal exposure to arsenic (through all three trimesters of fetal/neonatal development, DAE) has long-lasting consequences into adulthood including deficits in learning and memory, molecular aberrations in the hypothalamic-adrenal-pituitary (HPA) axis, and depressive-like symptoms in mice. The studies described in this dissertation were designed to assess the impact of DAE on adult hippocampal neurogenesis (AHN) as a possible mechanism of action …