College of Pharmacy, Yeungnam University, Gyeongsan-si, Gyeongsangbuk-do, 712-749, Korea.
Arch Pharm Res. 2011 Apr;34(4):661-9. doi: 10.1007/s12272-011-0417-4. Epub 2011 May 5.
Carbon nanotubes (CNTs), promising novel nanomaterials, have been applied to drug delivery and bio-imaging; however, their potential harmful effects on human health and environment have gained much attention recently. In the present study, we investigated cytotoxic effect of solubilized single-walled CNTs (SWCNTs), which were dispersed in water by sodium dodesyl sulfate (SDS), in normal rat kidney epithelial cells (NRK-52E). SDS-SWCNT (0.125-10 μg/mL)-treated NRK-52E cells showed decreased cell viability and enhanced cytotoxicity marker levels following 24-48 h incubation. In addition, SDS-SWCNT treatment evoked the cell growth inhibition: 8 μg/mL SDS-SWCNT induced the growth arrest at G(0)/G(1) phase and levels of cell cycle-related proteins such as CDK2, CDK6 and phosphorylated-retinoblastoma (pRB) were significantly reduced by CNT. Whereas, at higher concentration of SDS-SWCNT, the percentage of cell numbers in apoptotic sub-G(1) phase was substantially increased. Along with these changes, SDS-SWCNT treatment elevated protein levels for p53 and p21 with a concomitant increase in the single strand DNA breakage. Taken together, these results suggest that SDS-solubilized SWCNTs exert genotoxic effect in renal epithelial cells, and p53-dependent signaling can be associated with the growth arrest and apoptosis events upon CNT-induced DNA damage.
碳纳米管(CNTs)是一种很有前途的新型纳米材料,已被应用于药物输送和生物成像;然而,最近人们越来越关注它们对人类健康和环境的潜在有害影响。在本研究中,我们研究了溶解在十二烷基硫酸钠(SDS)中的单壁碳纳米管(SWCNTs)对正常大鼠肾上皮细胞(NRK-52E)的细胞毒性作用。SDS-SWCNT(0.125-10μg/mL)处理的 NRK-52E 细胞在孵育 24-48 小时后表现出细胞活力降低和细胞毒性标志物水平升高。此外,SDS-SWCNT 处理引起细胞生长抑制:8μg/mL SDS-SWCNT 诱导 G0/G1 期细胞停滞,细胞周期相关蛋白如 CDK2、CDK6 和磷酸化视网膜母细胞瘤(pRB)的水平显著降低。然而,在更高浓度的 SDS-SWCNT 下,细胞凋亡亚 G1 期的细胞数量百分比显著增加。随着这些变化,SDS-SWCNT 处理增加了 p53 和 p21 的蛋白水平,同时伴有单链 DNA 断裂的增加。总之,这些结果表明 SDS 溶解的 SWCNTs 在肾上皮细胞中具有遗传毒性作用,p53 依赖性信号通路可能与 CNT 诱导的 DNA 损伤引起的细胞生长停滞和细胞凋亡事件有关。