Title: Differential response of human T-lymphocytes to arsenic and uranium.
Authors: Dashner-Titus, Erica J; Schilz, Jodi R; Simmons, Karen A; Duncan, Tammi R; Alvarez, Sandra C; Hudson, Laurie G
Published In Toxicol Lett, (2020 Oct 15)
Abstract: Elevated levels of arsenic and uranium have been detected in water sources near abandoned uranium mines in the Southwest. Evidence suggests uranium exposure increases the likelihood of immune dysfunction and this study investigates the impact of arsenic and uranium on human immune cell lines. Concentration-dependent cytotoxicity occurred following exposure to arsenite, whereas cells remained viable after 48 -h treatment with up to 100 μM uranyl acetate despite uptake of uranium into cells. Arsenite stimulated an oxidative stress response as detected by Nrf-2 nuclear accumulation and induction of HMOX-1 and NQO1, which was not detected with up to 30 μM uranyl acetate. Cellular oxidative stress can promote DNA damage and arsenite, but not uranium, stimulated DNA damage as measured by pH2AX. Arsenic enhanced the cytotoxic response to etoposide suggesting an inhibition of DNA repair, unlike uranium. Similarly, uranium did not inhibit PARP-1 activity. Because uranium reportedly stimulates oxidative stress, DNA damage and cytotoxicity in adherent epithelial cells, the current study suggests distinct cell type differences in response to uranium that may relate to generation of oxidative stress and associated downstream consequences. Delineating the actions of uranium across different cell targets will be important for understanding the potential health effects of uranium exposures.
PubMed ID: 32866568
MeSH Terms: Arsenites/toxicity*; Biological Monitoring/methods; Cell Culture Techniques; Cell Survival/drug effects; Cell Survival/genetics; DNA Damage*; DNA Repair; Dose-Response Relationship, Drug; Gene Expression/drug effects; Humans; Jurkat Cells; Mining; Organometallic Compounds/metabolism; Organometallic Compounds/toxicity*; Oxidative Stress/drug effects*; Oxidative Stress/genetics; T-Lymphocytes/drug effects*; T-Lymphocytes/metabolism; T-Lymphocytes/pathology; THP-1 Cells; Water Pollutants, Chemical/toxicity*