Acute particulate hexavalent chromium exposure induces DNA double-strand breaks and activates homologous recombination repair in rat lung tissue.

Autor:	Lu H; Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States.; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States., Wise SS; Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States.; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States., Speer RM; Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States.; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States., Croom-Perez TJ; Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States.; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States., Toyoda JH; Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States.; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States., Meaza I; Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States.; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States., Williams A; Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States.; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States., Wise JP Jr; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States.; Pediatric Research Institute, University of Louisville, Louisville, KY 40292, United States., Kouokam JC; Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States.; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States., Young Wise J; Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States.; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States., Hoyle GW; Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY 40292, United States., Zhu C; West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610044, China., Ali AM; Earth and Planetary Sciences Department, The University of New Mexico, Albuquerque, NM 87131, United States., Wise JP Sr; Wise Laboratory of Environmental and Genetic Toxicology, Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States.; Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40292, United States.
Jazyk:	angličtina
Zdroj:	Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2024 Sep 01; Vol. 201 (1), pp. 1-13.
DOI:	10.1093/toxsci/kfae076
Abstrakt:	Hexavalent chromium [Cr(VI)] is an established human lung carcinogen, but the carcinogenesis mechanism is poorly understood. Chromosome instability, a hallmark of lung cancer, is considered a major driver of Cr(VI)-induced lung cancer. Unrepaired DNA double-strand breaks are the underlying cause, and homologous recombination repair is the primary mechanism preventing Cr(VI)-induced DNA breaks from causing chromosome instability. Cell culture studies show acute Cr(VI) exposure causes DNA double-strand breaks and increases homologous recombination repair activity. However, the ability of Cr(VI)-induced DNA breaks and repair impact has only been reported in cell culture studies. Therefore, we investigated whether acute Cr(VI) exposure could induce breaks and homologous recombination repair in rat lungs. Male and female Wistar rats were acutely exposed to either zinc chromate particles in a saline solution or saline alone by oropharyngeal aspiration. This exposure route resulted in increased Cr levels in each lobe of the lung. We found Cr(VI) induced DNA double-strand breaks in a concentration-dependent manner, with females being more susceptible than males, and induced homologous recombination repair at similar levels in both sexes. Thus, these data show this driving mechanism discovered in cell culture indeed translates to lung tissue in vivo. (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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