Evaluating long-term cellular effects of the arsenic species thio-DMAV: qPCR-based gene expression as screening tool |
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| Institution: | 1. Department of Psychosomatic Medicine and Psychotherapy, University Medical Center, Johannes Gutenberg-University, Untere Zahlbacher Str. 8, 55131 Mainz, Germany;2. Department of Behavioural Sciences and Learning, Linköping University, SE-581 83 Linköping, Sweden;3. Karolinska Institutet, Department of Clinical Neuroscience, Division of Psychiatry, SE-171 77 Stockholm, Sweden;4. Center for Courageous Living, 9300 Wilshire Boulevard, Suite #520, Beverly Hills, CA 90212, USA |
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| Abstract: | Thio-dimethylarsinic acid (thio-DMAV) is a human urinary metabolite of the class 1 human carcinogen inorganic arsenic as well as of arsenosugars. Thio-DMAV exerts strong cellular toxicity, whereas its toxic modes of action are not fully understood. For the first time, this study characterises the impact of a long-term (21 days) in vitro incubation of thio-DMAV on the expression of selected genes related to cell death, stress response, epigenetics and DNA repair. The observed upregulation of DNMT1 might be a cellular compensation to counterregulate the in a very recent study observed massive global DNA hypomethylation after chronic thio-DMAV incubation. Moreover, our data suggest that chronic exposure towards subcytotoxic, pico- to nanomolar concentrations of thio-DMAV causes a stress response in human urothelial cells. The upregulation of genes encoding for proteins of DNA repair (Apex1, Lig1, XRCC1, DDB2, XPG, ATR) as well as damage response (GADD45A, GADD45G, Trp53) indicate a potential genotoxic risk emanating from thio-DMAV after long-term incubation. |
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| Keywords: | Thio-dimethylarsinic acid Long-term cellular toxicity qPCR-based gene expression screening Cellular damage response |
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