{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:59:29Z","timestamp":1790762369068,"version":"4.1.0"},"reference-count":92,"publisher":"Wiley","issue":"8-9","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007546","name":"Agence Nationale de S\u00e9curit\u00e9 Sanitaire de l\u2019Alimentation, de l\u2019Environnement et du Travail","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007546","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Microcystins (MCs) are cyclic hepatotoxins produced by various species of cyanobacteria that inhibit serine\/threonine protein phosphatases. Their structure includes two variable amino acids, leading to 329 variants. MC\u2010LR was considered the most toxic variant and has been extensively investigated, other variants, differing in hydrophobicity, could possess unique behavior and toxicity. The aim of the current study was to compare the toxicity and genotoxicity of 3 MC variants (MC\u2010LR, \u2010RR and \u2010LF), in human liver HepaRG cells. Both undifferentiated and differentiated HepaRG cells were treated for 24\u2009h with concentrations up to 50\u2009\u03bcM for MC\u2010LR and \u2010RR and up to 6.25\u2009\u03bcM for MC\u2010LF. Using a high content analysis\u2010based approach, cell count and apoptosis (active caspase\u20103) were quantified, in addition to three markers of DNA damage: \u03b3H2AX, p53 phospho S15 and ATM phospho S1981. A significant increase in all these markers was observed in differentiated HepaRG cells, correlating with the onset of cytotoxicity. The potency of the three variants to induce micronuclei (MN) was further assessed in differentiated HepaRG cells after 24\u2009h of exposure to concentrations up to 25\u2009\u03bcM, revealing a concentration\u2010dependent increase with all variants. The responses in HepaRG cells treated with MC\u2010LF were consistently observed at lower concentrations compared to MC\u2010LR and MC\u2010RR across all endpoints investigated, including micronucleus formation and DNA damage markers. An increase of pH\u20093 staining was also observed with the 3 variants, suggesting an aneugenic effect. The higher in\u00a0vitro genotoxic potency of MC\u2010LF compared to MC\u2010LR needs to be confirmed in\u00a0vivo.<\/jats:p>","DOI":"10.1002\/em.70081","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:01:41Z","timestamp":1790758901000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparison of the Genotoxic Potential of Three Microcystin Variants (\u2010\n                    <scp>LR<\/scp>\n                    , \u2010\n                    <scp>RR<\/scp>\n                    , and \u2010\n                    <scp>LF<\/scp>\n                    ) by High Content Analysis and Micronucleus Assay in a Human Hepatic Cell Line"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5335-4553","authenticated-orcid":false,"given":"Rym","family":"Merabet","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Natural and Life 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