Apoptosis as a mechanism of human respiratory cell death upon exposure to carbon nanotubes

Introduction. Carbon nanotubes (CNTs) are a group of promising nanomaterials for industrial and biomedical applications. There has been shown influence of the physicochemical characteristics of CNTs on the toxic effects, including the ability to cause DNA damage and induce apoptosis. In this study, there was carried out a comparative assessment of pro-apoptotic effects under exposure to single-walled and multi-walled CNTs produced in Russia on human respiratory cells.

Materials and methods. Human bronchial epithelial cells BEAS-2B, alveolar epithelial cells A549, and lung fibroblasts MRC5-SV40 were exposed to pristine and purified TUBALL™ SWCNTs and Taunit-M MWCNTs. In cells exposed to 4 concentrations (100, 50, 0.03, 0.0006 μg/ml) of all types of CNTs for 72 hours, the level of mRNA of the P53, BAX and BCL2 genes, as well as the level of reactive oxygen species were assessed.

Results. All types of CNTs initiated apoptosis in human respiratory epithelial cells BEAS-2B and A549, but not in MRC5-SV40 lung fibroblasts. BEAS-2B were more sensitive to the effects of MWCNTs, while A549 were more sensitive to pristine SWCNTs. Apoptosis was initiated at low concentrations, including those corresponding to industrial exposures. The mechanism of oxidative stress could act as a factor in triggering apoptosis in lung epithelial cells.

Limitations. Relatively short (72 hours) cell incubation time and the use of 2D cell models that do not consider real cell interactions.

Conclusion. There were revealed differences in the mechanisms of initiation of the internal pathway of apoptosis and sensitivity to different types of CNTs depending on the type of epithelial cells. Comparative analysis of the initiation of apoptosis by different types of CNTs has shown that there are differences in potential target cells and toxic mechanisms, which should be considered in further studies.

Compliance with ethical standards. The study does not require the submission of a biomedical ethics committee opinion or other documents.

Contribution:
Fatkhutdinova L.M. — research design, data analysis, manuscript writing and editing;
Gabidinova G.F. — review of the literature, cell cultivation, cell tests, data processing, manuscript writing;
Dimiev A.M. — development of methods for preparing suspensions of materials for introduction into cells;
Valeeva E.V. — cell tests (gene expression);
Timerbulatova G.A. — review of the literature, cell cultivation, cell tests, summarizing the results obtained manuscript writing.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version

Conflict of interest. The authors declare no conflict of interest.

Acknowledgment. The study was supported by the Russian Science Foundation grant № 22-25-00512, https://rscf.ru/project/22-25-00512/

Received: October 12, 2023 / Accepted: November 15, 2023 / Published: December 8, 2023