Mechanisms related to carbon nanotubes genotoxicity in human cell lines of respiratory origin.

Autor: Fatkhutdinova LM; Kazan State Medical University, Kazan 420012, Russian Federation. Electronic address: liliya.fatkhutdinova@kazangmu.ru., Gabidinova GF; Kazan State Medical University, Kazan 420012, Russian Federation., Daminova AG; Kazan Federal University, Kazan 420008, Russian Federation., Dimiev AM; Kazan Federal University, Laboratory for Advanced Carbon Nanomaterials, Kazan 420008, Russian Federation., Khamidullin TL; Kazan Federal University, Laboratory for Advanced Carbon Nanomaterials, Kazan 420008, Russian Federation., Valeeva EV; Kazan State Medical University, Kazan 420012, Russian Federation., Cokou AEE; Kazan Federal University, Kazan 420008, Russian Federation., Validov SZ; Kazan Federal University, Kazan 420008, Russian Federation., Timerbulatova GA; Kazan State Medical University, Kazan 420012, Russian Federation.
Jazyk: angličtina
Zdroj: Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2024 Jan; Vol. 482, pp. 116784. Date of Electronic Publication: 2023 Dec 07.
DOI: 10.1016/j.taap.2023.116784
Abstrakt: Potential genotoxicity and carcinogenicity of carbon nanotubes (CNT), as well as the underlying mechanisms, remains a pressing topic. The study aimed to evaluate and compare the genotoxic effect and mechanisms of DNA damage under exposure to different types of CNT. Immortalized human cell lines of respiratory origin BEAS-2B, A549, MRC5-SV40 were exposed to three types of CNT: MWCNT Taunit-M, pristine and purified SWCNT TUBALL™ at concentrations in the range of 0.0006-200 μg/ml. Data on the CNT content in the workplace air were used to calculate the lower concentration limit. The genotoxic potential of CNTs was investigated at non-cytotoxic concentrations using a DNA comet assay. We explored reactive oxygen species (ROS) formation, direct genetic material damage, and expression of a profibrotic factor TGFB1 as mechanisms related to genotoxicity upon CNT exposure. An increase in the number of unstable DNA regions was observed at a subtoxic concentration of CNT (20 μg/ml), with no genotoxic effects at concentrations corresponding to industrial exposures being found. While the three test articles of CNTs exhibited comparable genotoxic potential, their mechanisms appeared to differ. MWCNTs were found to penetrate the nucleus of respiratory cells, potentially interacting directly with genetic material, as well as to enhance ROS production and TGFB1 gene expression. For A549 and MRC5-SV40, genotoxicity depended mainly on MWCNT concentration, while for BEAS-2B - on ROS production. Mechanisms of SWCNT genotoxicity were not so obvious. Oxidative stress and increased expression of profibrotic factors could not fully explain DNA damage under SWCNT exposure, and other mechanisms might be involved.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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