{
  "abstract": "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.",
  "abstract_shown": true,
  "affiliations": [
    "Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA.",
    "Wise Laboratory of Liver and Environmental Health, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA.",
    "NeuroWise Laboratory of Environmental Toxicology, University of Toledo, Toledo, OH 43614, USA.",
    "Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA.",
    "Mote Marine Laboratory, Sarasota, FL 34236, USA.",
    "Wise Laboratory of Nutritional Toxicology and Metabolism, University of Hawaii, Honolulu, HI 96822, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Idoia Meaza",
      "orcid": "0000-0001-5292-0843"
    },
    {
      "affs": [
        0
      ],
      "name": "Haiyan Lu",
      "orcid": "0000-0002-6711-0314"
    },
    {
      "affs": [
        1
      ],
      "name": "Jamie L Wise"
    },
    {
      "affs": [
        0
      ],
      "name": "Sandra Diven"
    },
    {
      "affs": [
        0
      ],
      "name": "Aggie W Brownell",
      "orcid": "0000-0001-5840-1585"
    },
    {
      "affs": [
        0
      ],
      "name": "John Easley",
      "orcid": "0009-0000-4964-1499"
    },
    {
      "affs": [
        0
      ],
      "name": "J Calvin Kouokam",
      "orcid": "0000-0001-8679-2536"
    },
    {
      "affs": [
        2
      ],
      "name": "John P Wise",
      "orcid": "0000-0002-9416-8570"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Samuel T Vielee"
    },
    {
      "affs": [
        5
      ],
      "name": "James T F Wise",
      "orcid": "0000-0002-8878-3841"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "John Pierce Wise",
      "orcid": "0000-0002-2587-2855"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5q5bxpsrw230y.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27198529",
  "fulltext_url": "https://europepmc.org/articles/PMC13664759",
  "id": "5q5bxpsrw230y",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://europepmc.org/article/MED/42883778",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2307|Chromium effects and bioremediation"
    ]
  ],
  "openalex": "W7214169728",
  "pdf_url": "https://europepmc.org/articles/PMC13664759?pdf=render",
  "pmcid": "PMC13664759",
  "pmid": "42883778",
  "published": "2026-09-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5q5bxpsrw230y.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:16Z",
      "native_id": "MED:42883778",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42883778"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2307|Chromium effects and bioremediation",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Mechanisms of Hexavalent Chromium-Induced Lung Carcinogenesis: DNA Double-Strand Breaks and DNA Repair Inhibition in a Guinea Pig Model.",
  "title_text": "Mechanisms of Hexavalent Chromium-Induced Lung Carcinogenesis: DNA Double-Strand Breaks and DNA Repair Inhibition in a Guinea Pig Model.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:16Z",
  "url": "https://research.draconitic.com/paper/5q5bxpsrw230y",
  "venue": "International journal of molecular sciences",
  "versions": []
}