Mechanisms of Hexavalent Chromium-Induced Lung Carcinogenesis: DNA Double-Strand Breaks and DNA Repair Inhibition in a Guinea Pig Model.
6 affiliations
- 1Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA.
- 2Wise Laboratory of Liver and Environmental Health, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA.
- 3NeuroWise Laboratory of Environmental Toxicology, University of Toledo, Toledo, OH 43614, USA.
- 4Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA.
- 5Mote Marine Laboratory, Sarasota, FL 34236, USA.
- 6Wise Laboratory of Nutritional Toxicology and Metabolism, University of Hawaii, Honolulu, HI 96822, USA.
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.
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BibTeX
@article{meaza2026mechanisms,
title = {{Mechanisms of Hexavalent Chromium-Induced Lung Carcinogenesis: DNA Double-Strand Breaks and DNA Repair Inhibition in a Guinea Pig Model.}},
author = {Idoia Meaza and Haiyan Lu and Jamie L Wise and Sandra Diven and Aggie W Brownell and John Easley and J Calvin Kouokam and John P Wise and Samuel T Vielee and James T F Wise and John Pierce Wise},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198529},
url = {https://europepmc.org/article/MED/42883778},
note = {CC BY},
}
RIS
TY - JOUR
TI - Mechanisms of Hexavalent Chromium-Induced Lung Carcinogenesis: DNA Double-Strand Breaks and DNA Repair Inhibition in a Guinea Pig Model.
AU - Idoia Meaza
AU - Haiyan Lu
AU - Jamie L Wise
AU - Sandra Diven
AU - Aggie W Brownell
AU - John Easley
AU - J Calvin Kouokam
AU - John P Wise
AU - Samuel T Vielee
AU - James T F Wise
AU - John Pierce Wise
PY - 2026
DA - 2026/09/24
JO - International journal of molecular sciences
DO - 10.3390/ijms27198529
UR - https://europepmc.org/article/MED/42883778
AB - 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.
SN - 1422-0067
ER -