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In Vitro Profiling Of Epigenetic Modifications Underlying Heavy Metal Toxicity Of Tungsten-Alloy And Its Components, Ranjana Verma, Xiufen Xu, Manoj K. Jaiswal, Cara Olsen, David Mears, Giuseppina Caretti, Zygmunt Galdzicki
In Vitro Profiling Of Epigenetic Modifications Underlying Heavy Metal Toxicity Of Tungsten-Alloy And Its Components, Ranjana Verma, Xiufen Xu, Manoj K. Jaiswal, Cara Olsen, David Mears, Giuseppina Caretti, Zygmunt Galdzicki
Uniformed Services University of the Health Sciences
Tungsten-alloy has carcinogenic potential as demonstrated by cancer development in rats with intramuscular implanted tungsten-alloy pellets. This suggests a potential involvement of epigenetic events previously implicated as environmental triggers of cancer. Here, we tested metal induced cytotoxicity and epigenetic modifications including H3 acetylation, H3-Ser10 phosphorylation and H3-K4 trimethylation. We exposed human embryonic kidney (HEK293), human neuroepithelioma(SKNMC), and mousemyoblast (C2C12) cultures for 1-day and hippocampal primary neuronal cultures for 1-week to 50–200 μg/ml of tungsten-alloy (91% tungsten/6% nickel/3% cobalt), tungsten, nickel, and cobalt. We also examined the potential role of intracellular calcium in metal mediated histone modifications by addition of calciumchannel …