{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:59:35Z","timestamp":1790398775305,"version":"4.1.0"},"reference-count":66,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Environmental Health Sciences","award":["R35ES032876"],"award-info":[{"award-number":["R35ES032876"]}],"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of Environmental Health Sciences","award":["R21-ES033327"],"award-info":[{"award-number":["R21-ES033327"]}],"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of Environmental Health Sciences","award":["T32ES011564"],"award-info":[{"award-number":["T32ES011564"]}],"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"crossref"}]},{"award":["R35ES032876"],"award-info":[{"award-number":["R35ES032876"]}],"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R21-ES033327"],"award-info":[{"award-number":["R21-ES033327"]}],"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"publisher"}]},{"award":["T32ES011564"],"award-info":[{"award-number":["T32ES011564"]}],"id":[{"id":"https:\/\/ror.org\/00j4k1h63","id-type":"ROR","asserted-by":"publisher"}]},{"name":"\u201cla Caixa\u201d Foundation, Spain","award":["LCF\/BQ\/EU22\/11930060"],"award-info":[{"award-number":["LCF\/BQ\/EU22\/11930060"]}]},{"name":"National Institutes of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Hexavalent chromium [Cr(VI)] is an environmental and occupational pollutant and a known lung carcinogen. Despite the exposure risks, it is unclear how Cr(VI) causes lung cancer. Prolonged Cr(VI) exposure induces DNA double-strand breaks and inhibits their repair in exposed cells, leading to chromosome instability, a hallmark of lung cancer. Specifically, Cr(VI) inhibits RAD51, a key effector protein in the homologous recombination repair pathway. The goal of this study was to translate this molecular mechanism of Cr(VI)-induced lung carcinogenesis to a guinea pig model. Hartley guinea pigs 10 to 11-week-old were exposed to zinc chromate via oropharyngeal aspiration for acute (24 h) or subchronic (90-day) exposure. Lungs were dissected and formalin-fixed paraffin-embedded. DNA double-strand breaks were measured using gamma-H2AX foci, and homologous recombination repair was assessed using RAD51 foci. Acute Cr(VI) exposure induced gamma-H2AX foci and RAD51 foci, whereas subchronic exposure also caused gamma-H2AX foci but inhibited RAD51 foci. These effects of Cr(VI)-induced DNA damage and repair inhibition were largely observed in bronchiolar regions but not in alveolar regions. This study establishes a new human-relevant model to study Cr(VI)-induced carcinogenesis and translates the mechanism of Cr(VI)-induced DNA double-strand break formation and repair inhibition to guinea pig lungs.<\/jats:p>","DOI":"10.3390\/ijms27198529","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:07:54Z","timestamp":1790240874000},"page":"8529","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanisms of Hexavalent Chromium-Induced Lung Carcinogenesis: DNA Double-Strand Breaks and DNA Repair Inhibition in a Guinea Pig Model"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5292-0843","authenticated-orcid":false,"given":"Idoia","family":"Meaza","sequence":"first","affiliation":[{"name":"Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6711-0314","authenticated-orcid":false,"given":"Haiyan","family":"Lu","sequence":"additional","affiliation":[{"name":"Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie L.","family":"Wise","sequence":"additional","affiliation":[{"name":"Wise Laboratory of Liver and Environmental Health, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Diven","sequence":"additional","affiliation":[{"name":"Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5840-1585","authenticated-orcid":false,"given":"Aggie W.","family":"Brownell","sequence":"additional","affiliation":[{"name":"Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4964-1499","authenticated-orcid":false,"given":"John","family":"Easley","sequence":"additional","affiliation":[{"name":"Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8679-2536","authenticated-orcid":false,"given":"J. Calvin","family":"Kouokam","sequence":"additional","affiliation":[{"name":"Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9416-8570","authenticated-orcid":false,"suffix":"Jr.","given":"John P.","family":"Wise","sequence":"additional","affiliation":[{"name":"NeuroWise Laboratory of Environmental Toxicology, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel T.","family":"Vielee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA"},{"name":"Mote Marine Laboratory, Sarasota, FL 34236, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8878-3841","authenticated-orcid":false,"given":"James T. F.","family":"Wise","sequence":"additional","affiliation":[{"name":"Wise Laboratory of Nutritional Toxicology and Metabolism, University of Hawaii, Honolulu, HI 96822, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2587-2855","authenticated-orcid":false,"suffix":"Sr.","given":"John Pierce","family":"Wise","sequence":"additional","affiliation":[{"name":"Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA"},{"name":"Wise Laboratory of Liver and Environmental Health, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"ref_1","first-page":"12","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. 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