Oxidative stress-mediated inhibition of intestinal epithelial cell proliferation by silver nanoparticles
Advisor:Waldman, W. James
cell cycle arrest
inhibition of cell proliferation
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Series/Report no.:2015 Edward F. Hayes Graduate Research Forum. 29th
Use of silver nanoparticles (NP) is of interest in the food and food packaging industries for their antimicrobial properties. In order to investigate potential consequences of Ag NP ingestion, this study was performed in the intestinal epithelial cell line C2BBe1. Ag NP were synthesized and characterized prior to biological experiments. The Ag NP had an average diameter of 23 nm as determined by TEM analysis. Treatment of proliferating cells (< 10,000 cells/cm2) with low doses of Ag NP (0.25 µg/cm2 or 1.25 µg/mL) for 24 hours induced 20% necrotic cell death and an 80% reduction in metabolic activity. Ag NP treatment of proliferating cells for 24 hours at 0.25 µg/cm2 induced oxidative stress in cells as indicated by a decrease in the GSH/GSSG ratio. Ag NP treatment with 0.25 µg/cm2 also induced G2/M phase cell cycle arrest and a complete inhibition of Ag NP. An in vitro digestion treatment of Ag NP prior to cell exposure required slightly higher doses (0.5 µg/cm2 or 2.5 µg/mL) to induce the same toxicity, likely due to increased species adsorbed to the surface causing slower Ag dissolution. Treatment of cells with silica, titania, and ZnO NP induced at least partial inhibition of cell proliferation at doses of 10 µg/cm2 (50 µg/mL), but the Ag NP-induced inhibition of cell proliferation at doses 40 times lower reveals a unique mechanism of Ag NP in these cells. Our results in proliferating cells suggest that Ag NP-induced oxidative stress leads to cell cycle arrest and the inhibition of cell proliferation. However, toxicity and induction of oxidative stress was not observed in confluent C2BBe1 cells (>100,000 cells/cm2) treated with up to 10 µg/cm2 (50 µg/mL) Ag NP, suggesting that these cells are not as sensitive to Ag NP. This is likely due to exposure of each cell to a smaller number of Ag NP when the cells are confluent in addition to decreased metabolic activity and increased resistance to toxic agents in confluent cells. Based on these studies, Ag NP ingestion may be able to slow proliferation of stem cells of the intestinal crypt and this is something that needs to be investigated further. The largest effects may be seen in diseased intestines where the epithelium is compromised.
Professional Biological Sciences: 1st Place (The Ohio State University Edward F. Hayes Graduate Research Forum)
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