Long‑term exposure of polyethylene nanoplastics promotes colorectal tumorigenesis

Abstract

Nanoplastics are emerging contaminants which can induce intestinal inflammation and dysfunction, yet their possible influence on colorectal tumorigenesis remains unclear. Here, six‑week‑old male mice were exposed to 125 mg/L 80 nm polyethylene nanoplastics, polyethylene nanoplastic/azoxymethane, polyethylene nanoplastics/azoxymethane/dextran sulfate sodium, and controls for 66 days. We assessed intestinal symptoms, colorectal tumorigenesis, and pathological, ultrastructural and molecular changes. Results show more colon tumors, of 18.3 versus 13.5, and heavier tumor burdens, of 113.1 versus 67.7 mm² in the mice treated with nanoplastics/azoxymethane/dextran sulfate sodium. Similarly, there were more colon tumors, of 6.0 versus 2.2, and heavier tumor burdens, of 26.0 versus 7.0 mm² in mice treated with nanoplastics/azoxymethane. Mice treated with nanoplastics alone developed colorectal neoplasms, of 2.9, with tumor burdens of 10.6 mm² and a pathology of polyp. Exposure to nanoplastics promoted tumor‑associated macrophages infiltration; disrupted microvilli, intercellular junctions, and the mitochondrial structures of colonic epithelium; and activated inflammation‑associated signaling pathways. Overall, the exposure to polyethylene nanoplastics facilitates the initiation and promotion of colorectal tumorigenesis, possibly by affecting mitochondrial structure and aggravating chronic colitis.