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Comprehensive gene expression in rat lung after inhalation exposure to C60 fullerene particles
Abstracts / Toxicology Letters 189S (2009) S57–S273
latter can take many years to emerge. Are workers exposed to nanomaterials in its manufacture and industrial use, and if so what are the characteristics and levels of exposure? How do nanoparticles interact with the body’s systems? Could nanotechnologies harm workers’ health and the environment? The lecture aims to provide an up-to-date view on potential sources of human exposure, on the standardization and physical–chemical characterization of nanoparticles in the light of cell–particle interactions and toxicological effects, on pulmonary and systemic toxicity, on the mechanisms of toxicity and evaluation of hazards to humans, as well as on the assessment and prevention of exposure to nanoparticles at the workplace and on the question whether existing regulation can cope with nanotechnology.
S179
New Energy and Industrial Technology Development Organization of Japan (NEDO) Grant (P06041). doi:10.1016/j.toxlet.2009.06.627
L04 Comparative pulmonary toxicity study of different size of crystalline silica in rats: Micron vs. nano-size Masato Naya ∗ , Norihiro Kobayashi, Makoto Ema, Junko Nakanishi Natl. Inst. Advanced Ind. Sci. Tech., Res. Inst. Safety and Sustainability, Tsukuba, Japan
doi:10.1016/j.toxlet.2009.06.626
L03 Comprehensive gene expression in rat lung after inhalation exposure to C60 fullerene particles Katsuhide Fujita 1,∗ , Yasuo Morimoto 2 , Akira Ogami 2 , Toshihiko Myojo 2 , Isamu Tanaka 2 , Manabu Shimada 3 , Wei-Ning Wang 3 , Shigehisa Endoh 4 , Kunio Uchida 4 , Tetsuya Nakazato 4 , Masaharu Inada 4 , Hiroaki Tao 4 , Kazuhiro Yamamoto 4 , Hiroko Fukui 5 , Masanori Horie 5 , Yasukazu Yoshida 5 , Hitoshi Iwahashi 5 , Junko Nakanishi 4 1 National Institute of Advanced Industrial Science and Technology, Health Technology Research Center, Tsukuba, Japan, 2 University of Occupational and Environmental Health, Institute of Industrial Ecological Sciences, Kitakyushu, Japan, 3 Hiroshima University, Higashi Hiroshima, Japan, 4 National Institute of Advanced Industrial Science, Tsukuba, Japan, 5 National Institute of Advanced Industrial Science, Health Technology Research Center, Osaka, Japan
Concern over the influence of nanoparticles on human health has risen due to advances in the development of nanotechnology. We are interested in the influence of nanoparticles on the pulmonary system at a molecular level. In this study, gene expression profiling of the rat lung after whole-body inhalation exposure to C60 fullerene (0.12 mg/m3 ; 4.1 × 104 particles/cm3 , 96 nm diameter) and ultrafine nickel oxide (Uf-NiO) particles (0.2 mg/m3 ; 9.2 × 104 particles/cm3 , 59 nm diameter) as a positive control were employed to gain insights into these molecular events. In response to C60 fullerene exposure for 6 h a day, for 4 weeks, C60 fullerene particles were located in alveolar epithelial cells at 3 days postexposure and engulfed by macrophages at both 3 days and 1 month post-exposures. Gene expression profiles revealed that few genes involved in the inflammatory response, oxidative stress, apoptosis, and metalloendopeptidase activity were up-regulated at both 3 days and 1 month post-exposure. Only some genes associated with the immune system process, including major histocompatibility complex-mediated immunity were up-regulated. These results were significantly different from those of Uf-NiO particles which induced high expression of genes associated with chemokines, oxidative stress, and matrix metalloproteinase 12 (Mmp12), suggesting that Uf-NiO particles lead to acute inflammation for the inhalation exposure period, and the damaged tissues were repaired in the post-exposure period. We suggest that C60 fullerene might not have a severe pulmonary toxicity under the inhalation exposure condition. Acknowledgements: This research was funded by
Lung toxicity induced by two different-sized crystalline silica particles was assessed in rats. The average primary size of these particles was approximately 128 nm, and 2.3 m, respectively. Groups of male Crl:CD (SD) rats were intratracheally instilled with 5 mg/kg of the crystalline silica particles. Following the instillations, the bronchoalveolar lavage fluid (BALF) of the rats was examined for inflammatory markers, and the histopathology of the lung, liver, spleen, and cerebrum at post-instillation timepoints of 24 h, 1 week, 4 weeks and 13 weeks was also examined. In all the groups, toxicological effects were observed only in the lung and not in the liver, spleen, or cerebrum. In the micron-silicainstilled group, the BALF revealed a significant increase in total cell and neutrophil numbers, LDH and protein concentrations, and TNF-␣ and MCP-1 activities. In the histopathological examination, macrophage accumulation and in inflammatory-cell infiltration in the alveoli, and hypertrophy of the alveolar epithelium cells were observed in the micron-silica-group up to 13 weeks after instillation. In the nano-silica-instilled group, the inflammatory responses were observed at 24 h, and then recovered by 4 weeks after instillation. These findings indicate that the pulmonary inflammatory responses in the group of micron-silica were severe than that of nano-silica group. doi:10.1016/j.toxlet.2009.06.628
L05 In vitro nanotoxicologic studies of silica-nanoparticles using dermal cell lines Tomoaki Yoshikawa 1,∗ , Hiromi Nabeshi 1,2,∗ , Keigo Matsuyama 1,2,∗ , Yasutaro Nakazato 1,2 , Takayoshi Imazawa 2 , Yasuo Yoshioka 1,2,3 , Yasuhiro Abe 2 , Yu-ichi Kawai 4 , Tadanori Mayumi 4 , Norio Itoh 1 , Shin-ichi Tsunoda 2,3 , Yasuo Tsutsumi 1,2,3,4 1
Osaka University, Graduate School of Pharmaceutical Sciences, Suita, Japan, 2 National Institute of Biomedical Innovation, Laboratory for Pharmaceutical Proteomics, Ibaraki, Japan, 3 Osaka University, The Center for Advanced Medical Engineering and Informatics, Suita, Japan, 4 Kobegakuin University, Faculty of Pharmaceutical Sciences, Kobe, Japan The recent development of nanoscale engineering represents a dynamic area of interdisciplinary research incorporating nanoparticles into a diverse product matrix, such as diagnostics, food additives, and cosmetics. Because the physicochemical properties and functions of these nanoparticles are related to their size and surface-to-volume ratios, more information regarding the toxicity of nanoparticles is urgently needed to ensure the health of workers and consumers. Further, the interaction of nanoparticles
latter can take many years to emerge. Are workers exposed to nanomaterials in its manufacture and industrial use, and if so what are the characteristics and levels of exposure? How do nanoparticles interact with the body’s systems? Could nanotechnologies harm workers’ health and the environment? The lecture aims to provide an up-to-date view on potential sources of human exposure, on the standardization and physical–chemical characterization of nanoparticles in the light of cell–particle interactions and toxicological effects, on pulmonary and systemic toxicity, on the mechanisms of toxicity and evaluation of hazards to humans, as well as on the assessment and prevention of exposure to nanoparticles at the workplace and on the question whether existing regulation can cope with nanotechnology.
S179
New Energy and Industrial Technology Development Organization of Japan (NEDO) Grant (P06041). doi:10.1016/j.toxlet.2009.06.627
L04 Comparative pulmonary toxicity study of different size of crystalline silica in rats: Micron vs. nano-size Masato Naya ∗ , Norihiro Kobayashi, Makoto Ema, Junko Nakanishi Natl. Inst. Advanced Ind. Sci. Tech., Res. Inst. Safety and Sustainability, Tsukuba, Japan
doi:10.1016/j.toxlet.2009.06.626
L03 Comprehensive gene expression in rat lung after inhalation exposure to C60 fullerene particles Katsuhide Fujita 1,∗ , Yasuo Morimoto 2 , Akira Ogami 2 , Toshihiko Myojo 2 , Isamu Tanaka 2 , Manabu Shimada 3 , Wei-Ning Wang 3 , Shigehisa Endoh 4 , Kunio Uchida 4 , Tetsuya Nakazato 4 , Masaharu Inada 4 , Hiroaki Tao 4 , Kazuhiro Yamamoto 4 , Hiroko Fukui 5 , Masanori Horie 5 , Yasukazu Yoshida 5 , Hitoshi Iwahashi 5 , Junko Nakanishi 4 1 National Institute of Advanced Industrial Science and Technology, Health Technology Research Center, Tsukuba, Japan, 2 University of Occupational and Environmental Health, Institute of Industrial Ecological Sciences, Kitakyushu, Japan, 3 Hiroshima University, Higashi Hiroshima, Japan, 4 National Institute of Advanced Industrial Science, Tsukuba, Japan, 5 National Institute of Advanced Industrial Science, Health Technology Research Center, Osaka, Japan
Concern over the influence of nanoparticles on human health has risen due to advances in the development of nanotechnology. We are interested in the influence of nanoparticles on the pulmonary system at a molecular level. In this study, gene expression profiling of the rat lung after whole-body inhalation exposure to C60 fullerene (0.12 mg/m3 ; 4.1 × 104 particles/cm3 , 96 nm diameter) and ultrafine nickel oxide (Uf-NiO) particles (0.2 mg/m3 ; 9.2 × 104 particles/cm3 , 59 nm diameter) as a positive control were employed to gain insights into these molecular events. In response to C60 fullerene exposure for 6 h a day, for 4 weeks, C60 fullerene particles were located in alveolar epithelial cells at 3 days postexposure and engulfed by macrophages at both 3 days and 1 month post-exposures. Gene expression profiles revealed that few genes involved in the inflammatory response, oxidative stress, apoptosis, and metalloendopeptidase activity were up-regulated at both 3 days and 1 month post-exposure. Only some genes associated with the immune system process, including major histocompatibility complex-mediated immunity were up-regulated. These results were significantly different from those of Uf-NiO particles which induced high expression of genes associated with chemokines, oxidative stress, and matrix metalloproteinase 12 (Mmp12), suggesting that Uf-NiO particles lead to acute inflammation for the inhalation exposure period, and the damaged tissues were repaired in the post-exposure period. We suggest that C60 fullerene might not have a severe pulmonary toxicity under the inhalation exposure condition. Acknowledgements: This research was funded by
Lung toxicity induced by two different-sized crystalline silica particles was assessed in rats. The average primary size of these particles was approximately 128 nm, and 2.3 m, respectively. Groups of male Crl:CD (SD) rats were intratracheally instilled with 5 mg/kg of the crystalline silica particles. Following the instillations, the bronchoalveolar lavage fluid (BALF) of the rats was examined for inflammatory markers, and the histopathology of the lung, liver, spleen, and cerebrum at post-instillation timepoints of 24 h, 1 week, 4 weeks and 13 weeks was also examined. In all the groups, toxicological effects were observed only in the lung and not in the liver, spleen, or cerebrum. In the micron-silicainstilled group, the BALF revealed a significant increase in total cell and neutrophil numbers, LDH and protein concentrations, and TNF-␣ and MCP-1 activities. In the histopathological examination, macrophage accumulation and in inflammatory-cell infiltration in the alveoli, and hypertrophy of the alveolar epithelium cells were observed in the micron-silica-group up to 13 weeks after instillation. In the nano-silica-instilled group, the inflammatory responses were observed at 24 h, and then recovered by 4 weeks after instillation. These findings indicate that the pulmonary inflammatory responses in the group of micron-silica were severe than that of nano-silica group. doi:10.1016/j.toxlet.2009.06.628
L05 In vitro nanotoxicologic studies of silica-nanoparticles using dermal cell lines Tomoaki Yoshikawa 1,∗ , Hiromi Nabeshi 1,2,∗ , Keigo Matsuyama 1,2,∗ , Yasutaro Nakazato 1,2 , Takayoshi Imazawa 2 , Yasuo Yoshioka 1,2,3 , Yasuhiro Abe 2 , Yu-ichi Kawai 4 , Tadanori Mayumi 4 , Norio Itoh 1 , Shin-ichi Tsunoda 2,3 , Yasuo Tsutsumi 1,2,3,4 1
Osaka University, Graduate School of Pharmaceutical Sciences, Suita, Japan, 2 National Institute of Biomedical Innovation, Laboratory for Pharmaceutical Proteomics, Ibaraki, Japan, 3 Osaka University, The Center for Advanced Medical Engineering and Informatics, Suita, Japan, 4 Kobegakuin University, Faculty of Pharmaceutical Sciences, Kobe, Japan The recent development of nanoscale engineering represents a dynamic area of interdisciplinary research incorporating nanoparticles into a diverse product matrix, such as diagnostics, food additives, and cosmetics. Because the physicochemical properties and functions of these nanoparticles are related to their size and surface-to-volume ratios, more information regarding the toxicity of nanoparticles is urgently needed to ensure the health of workers and consumers. Further, the interaction of nanoparticles