ArticleToxicological sciences : an official journal of the Society of Toxicology2016
Environmentally Relevant Concentrations of Arsenite Induce Dose-Dependent Differential Genotoxicity Through Poly(ADP-Ribose) Polymerase Inhibition and Oxidative Stress in Mouse Thymus Cells.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Chemical contaminants and environmental stressors induced teratogenic effect in aquatic ecosystem - A comprehensive review.Toxicology reports · 2024Review
- T'ah kóó hóniidló, we're still HERE! Mining legacies, Indigenous health and innovative solutions.Frontiers in public health · 2024Article
- Low-Energy Laser-Driven Ultrashort Pulsed Electron Beam Irradiation-Induced Immune Response in Rats.International journal of molecular sciences · 2021Article
- Modulation of PARP activity by Monomethylarsonous (MMAToxicology and applied pharmacology · 2021Article
- Exposures to uranium and arsenic alter intraepithelial and innate immune cells in the small intestine of male and female mice.Toxicology and applied pharmacology · 2020Article
- Zinc deficiency alters the susceptibility of pancreatic beta cells (INS-1) to arsenic exposure.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2019Article
- Exposure to arsenic in utero is associated with various types of DNA damage and micronuclei in newborns: a birth cohort study.Environmental health : a global access science source · 2019Article
- Minimal uranium immunotoxicity following a 60-day drinking water exposure to uranyl acetate in male and female C57BL/6J mice.Toxicology and applied pharmacology · 2019Article
- Differential sensitivities of cellular XPA and PARP-1 to arsenite inhibition and zinc rescue.Toxicology and applied pharmacology · 2017Article
- Genotoxicity induced by monomethylarsonous acid (MMAToxicology letters · 2017Article
- Biological effects and epidemiological consequences of arsenic exposure, and reagents that can ameliorate arsenic damageOncotarget · 2017Review
- Efflux Transporters Regulate Arsenite-Induced Genotoxicity in Double Negative and Double Positive T Cells.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Arsenic-contaminated freshwater: assessing arsenate and arsenite toxicity and low-dose genotoxicity in Gammarus elvirae (Crustacea; Amphipoda).Ecotoxicology (London, England) · 2017Article
- Combinatorial effects of zinc deficiency and arsenic exposure on zebrafish (Danio rerio) development.PloS one · 2017Article
- Differential sensitivities of bone marrow, spleen and thymus to genotoxicity induced by environmentally relevant concentrations of arsenite.Toxicology letters · 2016Article
- Editor's Highlight: Interactive Genotoxicity Induced by Environmentally Relevant Concentrations of Benzo(a)Pyrene Metabolites and Arsenite in Mouse Thymus Cells.Toxicological sciences : an official journal of the Society of Toxicology · 2016Article
- Environmentally relevant concentrations of arsenite and monomethylarsonous acid inhibit IL-7/STAT5 cytokine signaling pathways in mouse CD3+CD4-CD8- double negative thymus cells.Toxicology letters · 2016Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Inhibition of DNA repair and oxidative stress are 2 common mechanisms associated with arsenic-induced genotoxicity. The purpose of this study was to examine mechanisms of genotoxicity induced by environmentally relevant doses of arsenite (As(+3)) in mouse thymus cells. An increase in DNA damage and a decrease in poly(ADP-ribose) polymerase (PARP) activity were seen in vitro following exposure to 50 nM As(+3) in primary mouse thymus cells and a murine thymus pre-T cell line, D1. 3,4-Dihydro-5[4-(1-piperindinyl) butoxyl]-1(2H)-isoquinoline, a well-characterized PARP inhibitor, also produced DNA damage in D1 cells, confirming the correlation between PARP inhibition and DNA damage increase. As(+3) at 500 nM induced double strand breaks (DSBs) in DNA and oxidative stress at 4 h in D1 cells, which was reversed at 18 h. No apoptosis or decrease of viability was observed in these exposures. 4-Hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl, a widely-used antioxidant, was utilized to confirm that oxidative stress is partially responsible for the increase of strand breaks in 500 nM As(+3) exposure at 4 h. Expression of As(+3) exporters, Mdr1 and Mrp1, were found to be induced by 500 nM As(+3) in D1 cells, suggesting a possible mechanism for reversal of oxidative stress and DSBs at the 18-h timepoint. Finally, we showed that DNA damage and PARP inhibition by As(+3) were reversed by zinc (Zn(+2)) at approximate equimolar doses. Collectively, these results demonstrate that As(+3) at doses within the nanomolar range induce genotoxicity by inhibiting PARP, and produces oxidative stress at higher concentrations, which can be reversed by a Zn(+2) treatment.
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Registered trials
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