Health Technology Research Center, National Institute of Advanced Industrial Science and Technology, 1-8-31, Midorigaoka, Ikeda, Osaka 563-8577, Japan.
Chem Res Toxicol. 2009 Aug;22(8):1415-26. doi: 10.1021/tx900171n.
Nickel oxide (NiO) is one of the important industrial materials used in electronic substrates and for ceramic engineering. Advancements in industrial technology have enabled the manufacture of ultrafine NiO particles. On the other hand, it is well-known that nickel compounds exert toxic effects. The toxicity of nickel compounds is mainly caused by nickel ions (Ni(2+)). However, the ion release properties of ultrafine NiO particles are still unclear. In the present study, the influences of ultrafine NiO particles on cell viability were examined in vitro to obtain fundamental data for the biological effects of ultrafine green NiO and ultrafine black NiO. Ultrafine NiO particles showed higher cytotoxicities toward human keratinocyte HaCaT cells and human lung carcinoma A549 cells than fine NiO particles and also showed higher solubilities in culture medium (Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum) than fine NiO particles. In particular, the concentration of Ni(2+) released into the culture medium by ultrafine green NiO was 150-fold higher than that released by fine green NiO. The concentrations of Ni(2+) released by both types of NiO particles in an aqueous solution containing amino acids were remarkably higher than those released by NiO particles in water. Moreover, we prepared a uniform and stable dispersion of ultrafine black NiO in culture medium and examined its influence on cell viability in comparison with that of NiCl(2), a soluble nickel compound. A medium exchange after 6 h of exposure resulted in a loss of cytotoxicity in the cells exposed to NiCl(2), whereas cytotoxicity was retained in the cells exposed to NiO. Transmission electron microscope observations revealed uptake of both ultrafine and fine NiO particles into HaCaT cells. Taken together, the present results suggest that the intracellular Ni(2+) release could be an important factor that determines the cytotoxicity of NiO. Ultrafine NiO is more cytotoxic than fine NiO in vitro.
氧化镍 (NiO) 是一种重要的工业材料，用于电子基板和陶瓷工程。工业技术的进步使得制造超细微粒的 NiO 成为可能。另一方面，众所周知镍化合物具有毒性。镍化合物的毒性主要是由镍离子 (Ni(2+)) 引起的。然而，超细微粒 NiO 的离子释放特性尚不清楚。本研究在体外检测了超细微粒 NiO 对细胞活力的影响，以获得超细微粒绿 NiO 和超细微粒黑 NiO 的生物学效应的基础数据。超细微粒 NiO 对人角质形成细胞 HaCaT 细胞和人肺腺癌 A549 细胞的细胞毒性高于细粒 NiO，并且在培养基（含 10%胎牛血清的杜尔贝科改良伊格尔培养基）中的溶解度也高于细粒 NiO。特别是，超细微粒绿 NiO 释放到培养基中的 Ni(2+)浓度比细粒绿 NiO 高 150 倍。两种 NiO 颗粒在含有氨基酸的水溶液中释放的 Ni(2+)浓度明显高于在水中释放的 Ni(2+)浓度。此外，我们制备了均匀稳定的超细微粒黑 NiO 在培养基中的分散体，并与可溶性镍化合物 NiCl(2) 进行了细胞活力的比较。暴露 6 小时后更换培养基导致暴露于 NiCl(2)的细胞的细胞毒性丧失，而暴露于 NiO 的细胞的细胞毒性得以保留。透射电子显微镜观察显示两种超细微粒和细粒 NiO 均被 HaCaT 细胞摄取。综上所述，本研究结果表明，细胞内 Ni(2+)的释放可能是决定 NiO 细胞毒性的重要因素。超细微粒 NiO 在体外比细粒 NiO 更具细胞毒性。
