ZnO nanoparticles promote the malignant transformation of colorectal epithelial cells in APCmin/ plus mice
ZnO nanoparticles promote the malignant transformation of colorectal epithelial cells in APCmin/ plus mice
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ZnO纳米颗粒促进APC小鼠结直肠上皮细胞恶性转化
DOI：
10.1016/j.envint.2021.106923
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发表时间：
2021-10-08
影响因子：
11.8
通讯作者：
Cui，Shuxiang
中科院分区：
文献类型：
--
作者：
Meng，Jian;Yang，Juan;Cui，Shuxiang
随着氧化锌纳米颗粒（ZnO NPs）在日常产品中的使用越来越多，人们对健康风险的担忧也越来越多。然而，尚未发表关于ZnO纳米颗粒的胃肠道毒性的研究结果。我们使用APC min/+小鼠模型研究了ZnO纳米颗粒在小鼠结肠组织中可能的恶性转化，该模型具有肠上皮细胞的癌前病变。较高剂量和长期口服暴露于ZnO NPs被发现轻度促进WT小鼠的结肠炎症，而它们中度或强烈加重患有肠腺瘤性息肉病的APC min/+小鼠的慢性炎症和肿瘤发生的严重程度。ZnO NPs诱导的结肠上皮细胞炎症和肿瘤发生与CXCR 2/NF-κB/STAT 3/ERK和AKT通路的激活有关。对ZnO纳米颗粒加重APC min/+小鼠肠腺瘤性息肉病的分析表明，ZnO纳米颗粒可以激活APC驱动的Wnt/β-catenin信号通路，加重肠道肿瘤的发生。事实上，ZnO纳米颗粒已被证明通过释放游离Zn 2+增加APC min/+小鼠的肠道炎症和肿瘤发生。在WT小鼠中，低剂量的ZnO NPs（26 mg/kg/天）不会引起肠道炎症。总之，较高剂量和长期暴露于ZnO纳米颗粒促进癌前上皮细胞的恶性转化。
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 the possible malignant transformation of ZnO NPs in the mice’s colonic tissues using theAPCmin/+mouse model with a 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 inAPCmin/+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 inAPCmin/+mice revealed that ZnO NPs could activate theAPC-driven Wnt/β-catenin signaling pathway, exacerbating intestinal tumorigenesis. In fact, ZnO NPs have been shown to increase intestinal inflammation and tumorigenesis inAPCmin/+mice by releasing free Zn2+. In WT mice, a low dose of ZnO NPs (26 mg/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.