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Amorphous nanosilica induce endocytosis-dependent ROS generation and DNA damage in human keratinocytes

Hiromi Nabeshi1,2, Tomoaki Yoshikawa1,2*, Keigo Matsuyama1,2, Yasutaro Nakazato1,2, Saeko Tochigi1,2, Sayuri Kondoh1,2, Toshiro Hirai1,2, Takanori Akase1,2, Kazuya Nagano2, Yasuhiro Abe2, Yasuo Yoshioka2,3, Haruhiko Kamada2,3, Norio Itoh1, Shin-ichi Tsunoda1,2,3 and Yasuo Tsutsumi1,2,3*

Author Affiliations

1 Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan

2 Laboratory of Biopharamceutical Research (Pharmaceutical Proteomics), National Institute of Biomedical Innovation, 7-6-8, Saito-Asagi, Ibaraki, Osaka, 567-0085, Japan

3 The Center for Advanced Medical Engineering and Informatics, Osaka University, 1-6, Yamadaoka, Suita, Osaka, 565-0871, Japan

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Particle and Fibre Toxicology 2011, 8:1 doi:10.1186/1743-8977-8-1

Published: 15 January 2011

Abstract

Background

Clarifying the physicochemical properties of nanomaterials is crucial for hazard assessment and the safe application of these substances. With this in mind, we analyzed the relationship between particle size and the in vitro effect of amorphous nanosilica (nSP). Specifically, we evaluated the relationship between particle size of nSP and the in vitro biological effects using human keratinocyte cells (HaCaT).

Results

Our results indicate that exposure to nSP of 70 nm diameter (nSP70) induced an elevated level of reactive oxygen species (ROS), leading to DNA damage. A markedly reduced response was observed using submicron-sized silica particles of 300 and 1000 nm diameter. In addition, cytochalasin D-treatment reduced nSP70-mediated ROS generation and DNA damage, suggesting that endocytosis is involved in nSP70-mediated cellular effects.

Conclusions

Thus, particle size affects amorphous silica-induced ROS generation and DNA damage of HaCaT cells. We believe clarification of the endocytosis pathway of nSP will provide useful information for hazard assessment as well as the design of safer forms of nSPs.