>>ZnO nanoparticles promote the malignant transformation of colorectal epithelial cells in APCmin/+ mice

2025-04-22阅:10

题名:ZnO nanoparticles promote the malignant transformation of colorectal epithelial cells in APCmin/+ mice

来源:Science of The Total Environment

发表年代:2022

作者:Jian Meng, Juan Yang, Ting Pan, Xianjun Qu, Shuxiang Cui*

Abstract:As the use of zinc oxide nanoparticles (ZnO NPs) in everyday products  grows, so does concern about health risks.However, no findings on the  gastrointestinal toxicity of ZnO NPs have been published. We  investigated thepossible malignant transformation of ZnO NPs in the mice’s colonic tissues using the APCmin/+ mouse model witha premalignant  lesion in intestinal epithelial cells. Higher doses and long-term oral exposure to ZnO NPs were found to mildly promote colonic inflammation in  WT mice, while they moderately or strongly exacerbated the severity of  chronic inflammation and tumorigenesis in APCmin/+ mice with intestinal  adenomatous polyposis. The ZnO NPs-induced inflammation and tumorigenesis in colonic epithelial cells was linked to the activation  of CXCR2/NF-κB/STAT3/ERK and AKT pathways. Analysis of the ZnO  NPs-exacerbated intestinal adenomatous polyposis in APCmin/+ mice  revealed that ZnO NPs could activate the APC-driven Wnt/β-catenin  signaling pathway, exacerbating intestinal tumorigenesis. In fact, ZnO  NPs have been shown to increase intestinal inflammation and  tumorigenesis in APCmin/+ mice by releasing free Zn2+. In WT mice, a low  dose of ZnO NPs (26mg/kg/day) did not cause intestinal inflammation. In  conclusion, higher doses and prolonged exposure to ZnO NPs promote the  malignant transformation of precancerous epithelial cells.

ZnO nanoparticles promote the malignant transformation of colorectal epithelial cells in APCmin mice.pdf