Department of General Surgery, Hunan Provincial People's Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410005, China.
Food Science and Engineering, Central South University of Forestry and Technology, Changsha, Hunan 410004, China.
Ecotoxicol Environ Saf. 2024 Sep 15;283:116973. doi: 10.1016/j.ecoenv.2024.116973. Epub 2024 Aug 29.
Nano titanium dioxides (TiO) are widely used in drug development, food additives and packaging materials. Although several studies have demonstrated the poisonousness of TiO in vivo and in vitro, the underlying molecular mechanisms have not been fully revealed.
Characterization of TiO by FTIR, XRD, TEM and DLS. The NCM460 cell line, representing normal colon epithelial cells, was utilized as a model to assess the impact of TiO nanoparticles (TiO-NPs) on cell proliferation and apoptosis. The potential molecular mechanisms underlying its toxic effects were investigated through transcriptome analysis, RT-qPCR, and western blot experiments.
The particle size of the TiO-NPs used is about 25 nm, which has typical characteristics of anatase. TiO-NPs at a concentration of 30-60 μg/mL will cause changes in colon cell morphology, decreased proliferation ability, and increased number of apoptotic cells. TiO-NPs at a concentration of 6 μg/mL did not significantly modify the transcriptome expression profile of colon cells; while 30 μg/mL had a significant effect, leading to up-regulation of gene expression. The differentially expressed genes predominantly modulate the MAPK signaling pathway, TNF signaling pathway, cytokine-cytokine receptor interaction, and other related pathways. Further, western blot analysis revealed that higher concentrations of TiO-NPs (30-60 μg/mL) could up-regulate the expression of P53, P21 and Bax, while down-regulating the expression of Bcl2 by regulating the MAPK (ERK, P38) signaling pathway. Simultaneously, it also promoted the decreased in Fos protein expression and inhibited the phosphorylation of Jun and Fos.
This study demonstrates that TiO-NPs may exert potential toxic effects on colon cells, and therefore the intake of TiO-NPs should be strictly regulated in practical applications.
纳米二氧化钛（TiO）广泛应用于药物开发、食品添加剂和包装材料中。尽管有几项研究表明 TiO 在体内和体外具有毒性，但潜在的分子机制尚未完全揭示。
采用傅里叶变换红外光谱（FTIR）、X 射线衍射（XRD）、透射电子显微镜（TEM）和动态光散射（DLS）对 TiO 进行表征。以代表正常结肠上皮细胞的 NCM460 细胞系为模型，评估 TiO 纳米颗粒（TiO-NPs）对细胞增殖和凋亡的影响。通过转录组分析、RT-qPCR 和 Western blot 实验研究其毒性作用的潜在分子机制。
所使用的 TiO-NPs 的粒径约为 25nm，具有典型的锐钛矿特征。浓度为 30-60μg/ml 的 TiO-NPs 会引起结肠细胞形态改变、增殖能力下降和凋亡细胞增多。浓度为 6μg/ml 的 TiO-NPs 对结肠细胞的转录组表达谱没有明显改变；而 30μg/ml 则有显著影响，导致基因表达上调。差异表达基因主要调节 MAPK 信号通路、TNF 信号通路、细胞因子-细胞因子受体相互作用等相关通路。此外，Western blot 分析表明，较高浓度的 TiO-NPs（30-60μg/ml）通过调节 MAPK（ERK、P38）信号通路，上调 P53、P21 和 Bax 的表达，下调 Bcl2 的表达。同时，它还促进了 Fos 蛋白表达的减少，并抑制了 Jun 和 Fos 的磷酸化。
本研究表明，TiO-NPs 可能对结肠细胞产生潜在的毒性作用，因此在实际应用中应严格控制 TiO-NPs 的摄入。
