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Cytotoxicity and genotoxicity of titanium dioxide nanoparticles in UVA-irradiated normal peripheral blood lymphocytes

 Su Jin Kang  ;  Young Joon Lee  ;  Byeong Mo Kim  ;  Young Joo Choi  ;  Hai Won Chung 
 Drug and Chemical Toxicology, Vol.34(3) : 277-284, 2011 
Journal Title
 Drug and Chemical Toxicology 
Issue Date
Adult ; Apoptosis/drug effects ; Apoptosis/radiation effects ; Blotting, Western ; Cell Survival/drug effects ; Cell Survival/radiation effects ; Cells, Cultured ; DNA Damage ; Female ; Flow Cytometry ; Humans ; Lymphocytes/cytology ; Lymphocytes/drug effects* ; Lymphocytes/metabolism ; Lymphocytes/radiation effects ; Membrane Potential, Mitochondrial/drug effects ; Membrane Potential, Mitochondrial/radiation effects ; Micronuclei, Chromosome-Defective/chemically induced ; Micronuclei, Chromosome-Defective/radiation effects ; Micronucleus Tests ; Mutagenicity Tests ; Mutagens/chemistry ; Mutagens/toxicity* ; Nanoparticles* ; Photosensitizing Agents/chemistry ; Photosensitizing Agents/toxicity* ; Reactive Oxygen Species/metabolism ; Single-Cell Analysis ; Titanium/chemistry ; Titanium/toxicity* ; Ultraviolet Rays/adverse effects*
The phototoxicity of ultraviolet A irradiation (UVA) can be enhanced by photosensitizing agents, such as titanium dioxide nanoparticles (100 nm in diameter, "normal-TiO₂"). Nano-TiO₂ treatment in the absence of UVA caused a slight decrease in cell viability, but in the presence of UVA, it caused a significant decrease in cell viability. In the presence of UVA, nano-TiO₂ also significantly increased the percentage of the cell population in the sub-G₁ phase, induced activation of the proapoptotic proteins, caspase-9, caspase-3, and poly(ADP)ribose polymerase, significantly increased the production of reactive oxygen species (ROS), and induced the loss of the mitochondrial membrane potential (MMP), suggesting that UVA and nano-TiO₂ synergistically promoted apoptosis via a mitochondrial pathway. In the presence of UVA, but not in its absence, nano-TiO₂ treatment also caused a significant increase in DNA damage. Normal-TiO₂ used at the same concentrations did not cause DNA damage, induce ROS generation, trigger mitochondrial membrane depolarization, or increase apoptotic cell death, regardless of UVA exposure. Taken together, these results suggest that nano-TiO₂ and UVA synergistically promote rapid ROS generation and MMP collapse, triggering apoptosis. Additionally, they show that small TiO₂ particles are more phototoxic than larger ones.
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1. Journal Papers (연구논문) > 5. Research Institutes (연구소) > Yonsei Integrative Research Institute for Cerebral & Cardiovascular Disease (뇌심혈관질환융합연구사업단)
Yonsei Authors
김병모(Kim, Byeong Mo) ORCID logo https://orcid.org/0000-0002-0582-3132
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