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Therefore, the study aimed to determine the effects of TCE on cytotoxicity, apoptosis, reactive oxygen species (ROS) production, global histone modifications, and regulation in microRNAs (miRNAs) related to cancer pathways in human embryonic kidney cells (HEK\u2010293) after exposure to TCE at concentrations of 0.03, 0.1, and 0.3\u2009mM for 24\u2009h. Results indicated that TCE caused dose\u2010 dependent cytotoxicity without induction of significant apoptosis or ROS production at concentrations of \u2264\u20090.3\u2009mM. Upregulation in\n                    <jats:italic>myc<\/jats:italic>\n                    ,\n                    <jats:italic>pten<\/jats:italic>\n                    , and\n                    <jats:italic>mgmt<\/jats:italic>\n                    and downregulation in\n                    <jats:italic>ctnb1<\/jats:italic>\n                    ,\n                    <jats:italic>cd44<\/jats:italic>\n                    , and\n                    <jats:italic>cdkn2a<\/jats:italic>\n                    genes involved in cell cycle regulation and proliferation were detected. TCE decreased the expression of the\n                    <jats:italic>ezh2<\/jats:italic>\n                    gene and increased the expression of\n                    <jats:italic>riz1<\/jats:italic>\n                    and\n                    <jats:italic>hat1<\/jats:italic>\n                    genes, which are associated with chromatin\u2010modifying enzymes. Additionally, the levels of H3K27me3, H3K4me3, and H3K9me3 changed significantly. However, the alterations in global levels of H3K9ac were insignificant. TCE significantly altered the expression of approximately 25% of miRNAs related to cancer pathway in the miRNA array panel, as it upregulated 19 miRNAs and downregulated 4 miRNAs of the tested 84 miRNAs. Considering the effects on chromatin modification, proliferation rate, and miRNAs, it can be concluded that these mechanisms may be involved in TCE\u2010induced nephrotoxicity.\n                  <\/jats:p>","DOI":"10.1002\/jat.70090","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T23:29:31Z","timestamp":1770852571000},"page":"3018-3033","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Role of Histone Modifications and miRNA Regulations in the Toxicity of Trichloroethylene in Terms of Cell Cycle Regulation in Human Kidney Cells"],"prefix":"10.1002","volume":"46","author":[{"given":"Mahmoud","family":"Abudayyak","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ecem\u00a0Fatma","family":"Karaman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy Biruni University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeynep\u00a0Rana","family":"Guler","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy Istanbul University  Istanbul Turkey"},{"name":"Institute of Graduate Studies in Health Sciences Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6552-3457","authenticated-orcid":false,"given":"Tao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Public Health Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1662-2504","authenticated-orcid":false,"given":"Sibel","family":"\u00d6zden","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2020.114929"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/10934529.2015.1064275"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1525\u20101578(10)60532\u20106"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.868539"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476\u2010511X\u20105\u201010"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003\u20102697(76)90527\u20103"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.4014\/jmb.2108.08007"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02016"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2017.09.063"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.12659\/MSMBR.893608"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2021.127871"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2019.01.361"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1289\/ehp.1205879"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfw252"},{"key":"e_1_2_11_16_1","first-page":"185","volume-title":"Environmental Epigenomics in Health and Disease","author":"Cooney C. 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