{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:56:49Z","timestamp":1790848609083,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Iohexol is a nonionic, low\u2010osmolarity iodinated contrast agent that is widely used in clinical imaging applications. This study evaluated the cytotoxic effects and DNA damage responses of iohexol on the human breast adenocarcinoma cell line (MCF\u20107) in\u00a0vitro using MTS and alkaline comet assays. Additionally, molecular docking analyses were performed to complement this approach and investigate the potential interactions of iohexol with DNA, the anti\u2010apoptotic protein BCL\u2010XL, and the metabolic enzyme NUDT5. Iohexol administration caused a concentration\u2010dependent decrease in cell viability, with significant cytotoxicity observed at concentrations of \u2265\u200918.26\u2009mM (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001). Comet assay results showed increased DNA damage responses at concentrations above clinical doses, with significant increases detected from 22.8\u2009mM onwards (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05) and the highest damage levels observed at 91.3\u2013182.6\u2009mM (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01). Molecular docking analyses revealed that iohexol exhibited weak binding affinity with DNA (\u22123.57\u2009kcal\/mol), showing relatively more pronounced, albeit still moderate, interactions with BCL\u2010XL (\u22125.25\u2009kcal\/mol) and NUDT5 (\u22125.40\u2009kcal\/mol). These findings suggest that iohexol may indirectly interact via pathways associated with cellular stress. In general, the obtained data indicate that iohexol can cause cytotoxicity and DNA damage responses in MCF\u20107 cells under supra\u2010clinical in\u00a0vitro exposure conditions. These findings suggest that these effects develop through indirect cellular mechanisms rather than direct DNA binding. This emphasizes the need for careful interpretation of high\u2010dose in\u00a0vitro data, as well as the need for further mechanistic studies, in order to better understand the cellular effect profile of iohexol. Therefore, the present findings should not be interpreted as direct evidence of genotoxic risk under clinically relevant exposure conditions.\n                  <\/jats:p>","DOI":"10.1002\/jat.70340","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T04:57:48Z","timestamp":1784091468000},"page":"4223-4230","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Concentration\u2010Dependent Cytotoxicity and DNA Damage Responses of Iohexol in MCF\u20107 Breast Cancer Cells: An In\u00a0Vitro and In Silico Study"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0090-1311","authenticated-orcid":false,"given":"Ferhat","family":"Aslan","sequence":"first","affiliation":[{"name":"Obstetrics and Gynaecology Gaziantep Islam Science and Technology University  Gaziantep Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9848-954X","authenticated-orcid":false,"given":"\u0130brahim\u00a0Halil","family":"Kenger","sequence":"additional","affiliation":[{"name":"Medical Genetics Gaziantep Islam Science and Technology University  Gaziantep Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/741018"},{"issue":"1","key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.20492\/aeahtd.660381","article-title":"Kontrast Ajanlar; Farmakolojik \u00d6zellikleri, Genel Advers Reaksiyonlar\u0131 ve Ila\u00e7 Etkile\u015fimleri [Contrast Agents: Pharmacological Properties, General Adverse Reactions and Drug Interactions]","volume":"53","author":"Ayd\u0131n \u00d6. \u00c7.","year":"2020","journal-title":"Ankara E\u011fitim ve Ara\u015ft\u0131rma Hastanesi Dergisi"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.58600\/eurjther2576"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2023.166932"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241310945"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12010180"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxres\/tfaa093"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1667\/RADE-21-00178.1"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1076-6332(03)80456-7"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.rli.0000113776.87762.49"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2422060245"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/bcr2889"},{"key":"e_1_2_12_14_1","first-page":"594","volume-title":"Proceedings of the World Veterinary Orthopaedic Congress (WVOC 2010)","author":"Hong G.","year":"2010"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.4945"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1080\/01480545.2021.1878208"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.3109\/0886022X.2011.568146"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.4800"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/01480545.2023.2174988"},{"issue":"15","key":"e_1_2_12_20_1","first-page":"3071","article-title":"MCF\u20107: The First Hormone\u2010Responsive Breast Cancer Cell Line","volume":"57","author":"Levenson A. 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