Comparative study of cyto- and genotoxic potential with mechanistic insights of tungsten oxide nano- and microparticles in lung carcinoma cells.

Srinivas Chinde, Y Poornachandra, Archana Panyala, Srinivas Indu Kumari, Suresh Yerramsetty, Harikrishna Adicherla, Paramjit Grover

Journal: Journal of applied toxicology : JAT 2019;38(6):896-913

PMID: 29405315

Abstract

The exigency of semiconductor and super capacitor tungsten oxide nanoparticles (WO NPs) is increasing in various sectors. However, limited information on their toxicity and biological interactions are available. Hence, we explored the underlying mechanisms of toxicity induced by WO NPs and their microparticles (MPs) using different concentrations (0-300 μg ml ) in human lung carcinoma (A549) cells. The mean size of WO NPs and MPs by transmission electron microscopy was 53.84 nm and 3.88 μm, respectively. WO NPs induced reduction in cell viability, membrane damage and the degree of induction was size- and dose-dependent. There was a significant increase in the percentage tail DNA and micronuclei formation at 200 and 300 μg ml after 24 hours of exposure. The DNA damage induced by WO NPs could be attributed to increased oxidative stress and inflammation through reactive oxygen species generation, which correlated with the depletion of reduced glutathione content, catalase and an increase in malondialdehyde levels. Cellular uptake studies unveiled that both the particles were attached/surrounded to the cell membrane according to their size. In addition, NP inhibited the progression of the cell cycle in the G /M phase. Other studies such as caspase-9 and -3 and Annexin-V-fluorescein isothiocyanate revealed that NPs induced intrinsic apoptotic cell death at 200 and 300 μg ml concentrations. However, in comparison to NPs, WO MPs did not incite any toxic effects at the tested concentrations. Under these experimental conditions, the no-observed-significant-effect level of WO NPs was determined to be ≤200 μg ml in A549 cells.

Copyright © 2018 John Wiley & Sons, Ltd.

Address: Toxicology Unit, Pharmacology and Toxicology Division, Indian Institute of Chemical Technology, Hyderabad, Telangana, 500007, India.; Department of Genetics, Osmania University, Osmania University Main Road, Hyderabad, Telangana, 500007, India.; Flowcytometric Facility, Centre for Chemical Biology, Indian Institute of Chemical Technology, Hyderabad, Telangana, 500007, India.; Electron Microscopy Facility, Centre for Cellular and Molecular Biology, Habsiguda, Hyderabad, Telangana, 500007, India.

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