Silver nanoparticles-resistance of HeLa cell associated with its unusually high concentration of α-ketoglutarate and glutathione / 生物工程学报

Silver nanoparticles (AgNPs) is known as one of the most valuable metal nanoparticles in antibacterial and anticancer application. AgNPs-resistant bacteria has been documented, but it is unclear whether cancer cells can also escape the anti-cancer effect of AgNPs. In this study, we aimed to investigate this phenomenon and its underlying mechanism. The antibacterial activity and cytotoxicity of AgNPs were measured in the presence of HeLa cell metabolites. The status of AgNPs in the system associated with metabolites were characterized by UV-Vis, Zetasizer Nano ZS, and transmission electron microscopy. Non-targeted metabolomics was used to reveal the metabolites components that bind with AgNPs. HeLa cells were injected intraperitoneally to establish the tumor-bearing mice model, and the stability of AgNPs in mice serum was analyzed. The results manifested that HeLa cell metabolites inhibited the anticancer and antibacterial effects of AgNPs in a dose-dependent manner by causing AgNPs aggregation. Effective metabolites that inhibited the biological activity of AgNPs were stable in 100 ℃, insoluble in chloroform, containing sulfur elements, and had a molecular weight less than 1 kDa in molecular weight. There were 115 compounds bound with AgNPs. In vitro experiments showed that AgNPs aggregation occurred only when the concentration of α-ketoglutarate (AKG) and glutathione (GSH) together reached a certain threshold. Interestingly, the concentration of AKG and GSH in HeLa cellular metabolites was 10 and 6 times higher than that in normal cervical epithelial cells, respectively, which explained why the threshold was reached. Furthermore, the stability of AgNPs in the serum of tumor-bearing mice decreased by 20% (P < 0.05) compared with the healthy mice. In conclusion, our study demonstrates that HeLa cells escaped the anti-cancer effect of AgNPs through the synergistic effect of AKG and GSH, suggesting the need to develop strategies to overcome this limitation.

Effect of Air Formaldehyde Exposure of Medical Students on DNA-Protein Crosslinks in Their Buccal Mucosa Cells / 环境与健康杂志

Objective To study the effect of formaldehyde exposure on DNA-protein crosslinks (DPC) in buccal mucosa cells in students who were taking anatomy course.Methods The modified SDS-KCl precipitation assay published by Zhitkovich and Costa in 1992 was applied to detect DNA-protein crosslinks in human cells.And this method has been used to explore DPC induced by different pollutants in numerous studies.37 medical students (20 males and 17 females) aged 19.24?1.09 (mean?standard deviation) and 40 students (20 males and 20 females) in natural science college aged 19.55?0.99 (mean?standard deviation) were studied.The frequency of exposure to formaldehyde was 6 h per week in exposed group.Results Concentrations of formaldehyde in anatomy laboratory ranged from 0.42 to 1.57 mg/m3.Exposure to formaldehyde resulted in an increase of DNA-protein crosslinks.The percentage (mean?standard deviation) of DNA-protein crosslinks in exposed and nonexposed students were 25.72%?6.48% and 22.88%?5.34% respectively(P0.05).Conclusion The result of the present study suggests that formaldehyde exposure in medical students increases the frequency of DNA-protein crosslinks in buccal mucosa cells and females may be more sensitive to formaldehyde exposure.