دورية أكاديمية
Acute exposure to dihydroxyacetone promotes genotoxicity and chromosomal instability in lung, cardiac, and liver cell models.
| العنوان: | Acute exposure to dihydroxyacetone promotes genotoxicity and chromosomal instability in lung, cardiac, and liver cell models. |
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| المؤلفون: | Hernandez A; Department of Pharmacology and Toxicology, The University of Alabama at Birmingham, 1720 2nd Ave S, Birmingham, AL, 35294, USA., Hedlich-Dwyer J; Department of Pharmacology and Toxicology, The University of Alabama at Birmingham, 1720 2nd Ave S, Birmingham, AL, 35294, USA., Hussain S; Department of Pharmacology and Toxicology, The University of Alabama at Birmingham, 1720 2nd Ave S, Birmingham, AL, 35294, USA., Levi H; Department of Pharmacology and Toxicology, The University of Alabama at Birmingham, 1720 2nd Ave S, Birmingham, AL, 35294, USA., Sonavane M; Department of Pharmacology and Toxicology, The University of Alabama at Birmingham, 1720 2nd Ave S, Birmingham, AL, 35294, USA., Suzuki T; Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan., Kamiya H; Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan., Gassman NR; Department of Pharmacology and Toxicology, The University of Alabama at Birmingham, 1720 2nd Ave S, Birmingham, AL, 35294, USA. |
| المصدر: | Toxicological sciences : an official journal of the Society of Toxicology [Toxicol Sci] 2024 Jun 12. Date of Electronic Publication: 2024 Jun 12. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: United States NLM ID: 9805461 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1096-0929 (Electronic) Linking ISSN: 10960929 NLM ISO Abbreviation: Toxicol Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1999- : Cary, NC : Oxford University Press Original Publication: Orlando, FL : Academic Press, c1998- |
| مستخلص: | Inhalation exposures to dihydroxyacetone (DHA) occur through spray tanning and e-cigarette aerosols. Several studies in skin models have demonstrated that millimolar doses of DHA are cytotoxic, yet the genotoxicity was unclear. We examined the genotoxicity of DHA in cell models relevant to inhalation exposures. Human bronchial epithelial cells BEAS-2B, lung carcinoma cells A549, cardiomyocyte Ac16, and hepatocellular carcinoma HepG3 were exposed to DHA, and low millimolar doses of DHA were cytotoxic. IC90 DHA doses induced cell cycle arrest in all cells except the Ac16. We examined DHA's genotoxicity using strand break markers, DNA adduct detection by Repair Assisted Damage Detection (RADD), metaphase spreads, and a forward mutation assay for mutagenesis. Similar to results for skin, DHA did not induce significant levels of strand breaks. However, RADD revealed DNA adducts were induced 24 h after DHA exposure, with BEAS-2B and Ac16 showing oxidative lesions and A549 and HepG3 showing crosslink-type lesions. Yet, only low levels of reactive oxygen species or advanced glycation end products were detected after DHA exposure. Metaphase spreads revealed significant increases in chromosomal aberrations in the BEAS-2B and HepG3 with corresponding changes in ploidy. Finally, we confirmed the mutagenesis observed using the supF reporter plasmid. DHA increased the mutation frequency, consistent with methylmethane sulfonate, a mutagen and clastogen. These data demonstrate DHA is a clastogen, inducing cell-specific genotoxicity and chromosomal instability. The specific genotoxicity measured in the BEAS-2B in this study suggests that inhalation exposures pose health risks to vapers, requiring further investigation. (© 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.) |
| تواريخ الأحداث: | Date Created: 20240613 Latest Revision: 20240613 |
| رمز التحديث: | 20240613 |
| DOI: | 10.1093/toxsci/kfae075 |
| PMID: | 38867704 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1096-0929 |
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| DOI: | 10.1093/toxsci/kfae075 |