Exposure to nano-size titanium dioxide causes oxidative damages in human mesothelial cells: The crystal form rather than size of particle contributes to cytotoxicity

Our plain-English summary of Exposure to nano-size titanium dioxide causes oxidative damages in human mesothelial cells: The crystal form rather than size of particle contributes to cytotoxicity, by K. Hattori, K. Nakadate, A. Morii, et al (Biochemical and Biophysical Research Communications, 2017).

The study

• Authors: K. Hattori, K. Nakadate, A. Morii, T. Noguchi, Y. Ogasawara, K. Ishii
• Journal: Biochemical and Biophysical Research Communications
• Published: 2017;492(2):218-223
• Cited by: 14 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Exposure to nanoparticles such as carbon nanotubes has been shown to cause pleural mesothelioma similar to that caused by asbestos, and has become an environmental health issue. Not only is the percutaneous absorption of nano-size titanium dioxide particles frequently considered problematic, but the possibility of absorption into the body through the pulmonary route is also a concern. Nevertheless, there are few reports of nano-size titanium dioxide particles on respiratory organ exposure and dynamics or on the mechanism of toxicity. In this study, we focused on the morphology as well as the size of titanium dioxide particles. In comparing the effects between nano-size anatase and rutile titanium dioxide on human-derived pleural mesothelial cells, the anatase form was shown to be actively absorbed into cells, producing reactive oxygen species and causing oxidative damage to DNA. In contrast, we showed for the first time that the rutile form is not easily absorbed by cells and, therefore, does not cause oxidative DNA damage and is significantly less damaging to cells. These results suggest that with respect to the toxicity of titanium dioxide particles on human-derived mesothelial cells, the crystal form rather than the particle size has a greater effect on cellular absorption. Also, it was indicated that the difference in absorption is the primary cause of the difference in the toxicity against mesothelial cells.

Copyright © 2017 Elsevier Inc. All rights reserved.

In plain English

This was a laboratory study of cells grown in dishes, not of people, and it tested titanium dioxide, not asbestos. The authors, from Meiji Pharmaceutical University in Tokyo, exposed a commercial line of human pleural mesothelial cells (MeT-5A) to three kinds of titanium dioxide particles: nano-size anatase, nano-size rutile, and larger fine-particle anatase. At 200 µg/mL for 48 hours, only nano-size anatase caused significant cell damage compared with untreated cells. At 100 µg/mL, nano-size anatase raised reactive oxygen species about 2.5-fold compared with nano-size rutile. It was also the only particle that significantly raised a marker of oxidative DNA damage (8-OHdG) at 24 hours. Under the electron microscope, all cells exposed to nano-size anatase took up the particles. Only a small number of cells took up fine anatase, and no uptake of nano-size rutile was seen. After 48 hours with nano-size anatase, most cells looked unhealthy, especially the nuclear membrane. The authors concluded that the two crystal forms differed significantly in biological effects, and suggested that the anatase form could possibly cause health damage.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) cell-culture experiment
• Who was studied: A human pleural mesothelial cell line (MeT-5A) bought from the American Type Culture Collection. No people or animals were studied. The authors are at Meiji Pharmaceutical University, Tokyo, and no dates are given for the experiments.
• Exposure: Titanium dioxide particles, not asbestos. Three types were tested: nano-size anatase, nano-size rutile, and fine-particle anatase. Doses were mainly 100 and 200 µg/mL, for periods from 15 minutes up to 48 hours.
• Main results:
  • Nano-size anatase caused significant cell damage (LDH leakage) after 48 hours compared with untreated control cells.
  • At 200 µg/mL, nano-size rutile and fine-particle anatase caused no significant LDH leakage.
  • For nano-size anatase, released LDH was about 5% of total LDH, and the damage increased with dose and time.
  • At 100 µg/mL, after 2 to 8 hours, nano-size anatase increased reactive oxygen species 2.5-fold compared with nano-size rutile.
  • Reactive oxygen species from nano-size anatase rose with dose after 8 or 24 hours.
  • After 24 hours at 100 µg/mL, only nano-size anatase significantly increased the oxidative DNA damage marker 8-OHdG compared with untreated cells.
  • The authors stated that 8-OHdG formation was not simply correlated with reactive oxygen species formation.
  • Under the electron microscope after 24 hours, all cells exposed to nano-size anatase had taken up a considerable amount of particles into the cytoplasm.
  • With fine-particle anatase, a small number of cells took up particles, but most cells did not.
  • With nano-size rutile, no cell uptake of particles was observed.
  • After 48 hours of exposure to nano-size anatase, most cells did not have healthy structure, especially the nuclear membrane.
  • After 48 hours with nano-size anatase, many autophagosome-like structures or vacuoles were seen in most cells.
• The authors' conclusion: The authors concluded that anatase and rutile nano-size titanium dioxide differed significantly in biological effects, including genotoxic potential. They suggested that use of the anatase form has the possibility to cause health damage.

Topics

Medical terms in this study, explained in our Lexicon: Damages, Mesothelial Cells, Pleural Mesothelioma, Reactive Oxygen Species (ROS).

Related studies

• Oxidative stress-mediated cytotoxicity and apoptosis induction by TiO2 nanofibers in HeLa cells — K.M. Ramkumar, C. Manjula, et al. (2012)
• Phagocytosis of crocidolite asbestos induces oxidative stress, DNA damage, and apoptosis in mesothelial cells — W. Liu, J.D. Ernst, et al. (2000)
• Cytotoxicity, oxidative stress and genotoxicity induced by glass fibers on human alveolar epithelial cell line A549 — V. Rapisarda, C. Loreto, et al. (2015)
• Tobacco smoke: involvement of reactive oxygen species and stable free radicals in mechanisms of oxidative damage, carcinogenesis and synergistic effects with other respirable particles — A. Valavanidis, T. Vlachogianni, et al. (2009)
• Detection of 8-oxo-2'-deoxyguanosine, a marker of oxidative DNA damage, in culture medium from human mesothelial cells exposed to crocidolite asbestos — Q. Chen, J. Marsh, et al. (1996)
• Mechanisms of oxidative stress and alterations in gene expression by Libby six-mix in human mesothelial cells — J.M. Hillegass, A. Shukla, et al. (2010)

Browse more research in Biochemical and Biophysical Research Communications, or return to medical research.