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

Cytotoxicity and genotoxicity of titanium dioxide nanoparticles in UVA-irradiated normal peripheral blood lymphocytes
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DOI:
10.3109/01480545.2010.546800
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发表时间:
2011-07-01
影响因子:
2.6
通讯作者:
Chung, Hai Won
Chung, Hai Won
中科院分区:
医学4区
文献类型:
--
作者:
Kang, Su Jin;Lee, Young Joon;Chung, Hai Won

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紫外线A照射(UVA)的光毒性可以通过光敏剂增强,例如二氧化钛纳米颗粒(直径100 nm,“正常-TiO 2”)。纳米二氧化钛治疗在UVA的情况下引起细胞活力略有下降,但在UVA的存在下,它引起细胞活力的显着下降。在UVA存在下,nano-TiO 2还显著增加亚G1期细胞群体的百分比,诱导促凋亡蛋白caspase-9、caspase-3和聚(ADP)核糖聚合酶的活化,显著增加活性氧(ROS)的产生,并诱导线粒体膜电位(MMP)的丧失,表明UVA和纳米TiO 2通过线粒体途径协同促进细胞凋亡。在UVA的存在下,而不是在其不存在下,纳米TiO 2处理也引起了DNA损伤的显着增加。无论UVA暴露如何,在相同浓度下使用的正常TiO 2不会引起DNA损伤、诱导ROS产生、触发线粒体膜去极化或增加凋亡细胞死亡。总之,这些结果表明,纳米TiO 2和UVA协同促进快速ROS生成和MMP崩溃,引发细胞凋亡。此外,他们表明,小的TiO 2颗粒比大的颗粒更具有光毒性。
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-G 1 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.