{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T14:05:20Z","timestamp":1770818720856,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T00:00:00Z","timestamp":1721174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Faculty of Pharmacy and Biochemistry, University of Zagreb","award":["KK.01.1.1.02.0021"],"award-info":[{"award-number":["KK.01.1.1.02.0021"]}]},{"name":"European Regional Development Fund","award":["KK.01.1.1.02.0021"],"award-info":[{"award-number":["KK.01.1.1.02.0021"]}]},{"name":"University of Zagreb","award":["KK.01.1.1.02.0021"],"award-info":[{"award-number":["KK.01.1.1.02.0021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Citrinin (CIT), a polyketide mycotoxin produced by Penicillium, Aspergillus, and Monascus species, is a contaminant that has been found in various food commodities and was also detected in house dust. Several studies showed that CIT can impair the kidney, liver, heart, immune, and reproductive systems in animals by mechanisms so far not completely elucidated. In this study, we investigated the CIT mode of action on two human tumor cell lines, HepG2 (hepatocellular carcinoma) and A549 (lung adenocarcinoma). Cytotoxic concentrations were determined using an MTT proliferation assay. The genotoxic effect of sub-IC50 concentrations was investigated using the alkaline comet assay and the impact on the cell cycle using flow cytometry. Additionally, the CIT effect on the total amount and phosphorylation of two cell-cycle-checkpoint proteins, the serine\/threonine kinase Chk2 and Fanconi anemia (FA) group D2 (FANCD2), was determined by the cell-based ELISA. The data were analyzed using GraphPad Prism statistical software. The CIT IC50 for HepG2 was 107.3 \u00b5M, and for A549, it was &gt;250 \u00b5M. The results showed that sensitivity to CIT is cell-type dependent and that CIT in sub-IC50 and near IC50 induces significant DNA damage and cell-cycle arrest in the G2\/M phase, which is related to the increase in total and phosphorylated Chk2 and FANCD2 checkpoint proteins in HepG2 and A549 cells.<\/jats:p>","DOI":"10.3390\/toxins16070321","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T12:29:43Z","timestamp":1721219383000},"page":"321","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Citrinin Provoke DNA Damage and Cell-Cycle Arrest Related to Chk2 and FANCD2 Checkpoint Proteins in Hepatocellular and Adenocarcinoma Cell Lines"],"prefix":"10.3390","volume":"16","author":[{"given":"Darija","family":"Stupin Polan\u010dec","sequence":"first","affiliation":[{"name":"OnkoLab Ltd., 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja","family":"Homar","sequence":"additional","affiliation":[{"name":"University of Zagreb Faculty of Pharmacy and Biochemistry, Department of Biochemistry and Molecular Biology, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Jak\u0161i\u0107","sequence":"additional","affiliation":[{"name":"University of Zagreb Faculty of Pharmacy and Biochemistry, Department of Microbiology, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3117-2847","authenticated-orcid":false,"given":"Nevenka","family":"Kopjar","sequence":"additional","affiliation":[{"name":"Mutagenesis Unit, Institute for Medical Research and Occupational Health, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1923-6542","authenticated-orcid":false,"given":"Maja","family":"\u0160egvi\u0107 Klari\u0107","sequence":"additional","affiliation":[{"name":"University of Zagreb Faculty of Pharmacy and Biochemistry, Department of Microbiology, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanja","family":"Dabeli\u0107","sequence":"additional","affiliation":[{"name":"University of Zagreb Faculty of Pharmacy and Biochemistry, Department of Biochemistry and Molecular Biology, 10000 Zagreb, Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"457","DOI":"10.2478\/10004-1254-60-2009-1992","article-title":"Toxicological properties of citrinin","volume":"60","author":"Flajs","year":"2009","journal-title":"Arh. 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