{"refrec":{"BRefID":339737,"RR":"<b>Verma, R.; Xu, X.; Jaiswal, M.K.; Olsen, C.; Mears, D.; Caretti, G.; Galdzicki, Z.</b> (2011). In vitro profiling of epigenetic modifications underlying heavy metal toxicity of tungsten-alloy and its components. <i>Toxicol. Appl. Pharmacol. 253(3)</i>: 178-187. <a href=\"https://dx.doi.org/10.1016/j.taap.2011.04.002\" target=\"_blank\">https://dx.doi.org/10.1016/j.taap.2011.04.002</a>","BEntID":336372,"PublicFlag":1,"CheckedFlag":0,"wosflag":1,"vabbflag":1,"RefStringPartII":". <i>Toxicol. Appl. Pharmacol. 253(3)</i>: 178-187. <a href=\"https://dx.doi.org/10.1016/j.taap.2011.04.002\" target=\"_blank\">https://dx.doi.org/10.1016/j.taap.2011.04.002</a>","DocTypID":8,"DocType":"Journal article","MarineFlag":0,"FreshFlag":0,"BrackishFlag":0,"TerrestrialFlag":0,"Authorstring":"Verma, R.; Xu, X.; Jaiswal, M.K.; Olsen, C.; Mears, D.; Caretti, G.; Galdzicki, Z.","OrigTitleTranslFlag":0,"Authorstringtrunc":"Verma, R. <i>et al.</i>","Englishabstract":"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 mouse myoblast (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 calcium channel blockers/chelators to the metal solutions. Tungsten and its alloy showed cytotoxicity at concentrations > 50 μg/ml, while we found significant toxicity with cobalt and nickel for most tested concentrations. Diverse cell-specific toxic effects were observed, with C2C12 being relatively resistant to tungsten-alloy mediated toxic impact. Tungsten-alloy, but not tungsten, caused almost complete dephosphorylation of H3-Ser10 in C2C12 and hippocampal primary neuronal cultures with H3-hypoacetylation in C2C12. Dramatic H3-Ser10 dephosphorylation was found in all cobalt treated cultures with a decrease in H3 pan-acetylation in C2C12, SKNMC and HEK293. Trimethylation of H3-K4 was not affected. Both tungsten-alloy and cobalt mediated H3-Ser10 dephosphorylation were reversed with BAPTA-AM, highlighting the role of intracellular calcium, confirmed with 2-photon calcium imaging. In summary, our results for the first time reveal epigenetic modifications triggered by tungsten-alloy exposure in C2C12 and hippocampal primary neuronal cultures suggesting the underlying synergistic effects of tungsten, nickel and cobalt mediated by changes in intracellular calcium homeostasis and buffering.","AbstractOtherLang":null,"BibLvlCode":"AS","StandardTitle":"In vitro profiling of epigenetic modifications underlying heavy metal toxicity of tungsten-alloy and its components","OrigTitleLangCode":"en","OrigTitleLangCodeExtended":"eng","OrigTitleLangID":15,"DateLastModified":{"date":"2026-06-08 01:31:24.238052","timezone_type":1,"timezone":"+02:00"},"UserAccessRight":null,"UserAccID":null,"AuthorKeywords":"Tungsten-alloy; H3-histone modifications; Cytotoxicity; Epigenetics; Calcium channel blockers; Calcium chelators 2-photon calcium imaging","OtherDescriptors":null,"Notes":null,"AnaPub":2011,"MonPub":null,"DateUpdate":"2021-07-06","DateCreate":"2021-07-06","SecASFANote":null,"ConfID":null,"PeerRev":1,"VlizCoreFlag":1,"WoScode":"WOS:000291372000003","VABBcode":null,"OpenAcc":0,"DOI":"10.1016/j.taap.2011.04.002"},"refs":null,"anarec":{"AnaID":339737,"PubliDate":2011,"Pagination":"178-187","XtraPublOfAnaID":null,"ISBN":null,"Volume":"253","Issue":"3","BRefMon":null,"BRefMonRR":null,"BRefXtra":null,"BRefXtraRR":null,"SerBRefID":44053,"SerRR":"Toxicology and applied pharmacology. 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