摘要
Halobenzoquinones(HBQs),a class of water dis-infection byproducts(DBPs),have emerged as potential bladder carcinogens.However,evidence regarding the long-term health effects of HBQexposure and their potential to induce malignant trans-formation remains limited.Here,we examined the chronic effects of 2,6-dichlorobenzoquinone(2,6-DCBQ)exposure on human immor-talized uroepithelial cells(SV-HUC-1),with a focus on malignant transformation.Cells were continuously exposed to a noncytotoxic concentration of 2,6-DCBQfor over three months.The long-term transformed cells exhibited cellular and nuclear pleomorphism and anchorage-independent cell growth—a hallmark of cancer cell transformation.Proteomic analysis identified 60 differentially ex-pressed proteins(DEPs),20 of which are strongly associated with specific pathways of urinary bladder and urothelial cells.Enrichment analysis highlighted the actin cytoskeleton and extracellular matrix(ECM)-receptor interaction pathways.These molecular changes were supported by immunofluorescence assay,revealing filamentous actin disorganization and vinculin mislocalization in 2,6-DCBQ-treated cells.Together,these results suggest that cytoskeletal destabilization and adhesion collapse are key features associated with 2,6-DCBQ-induced malignant transformation,indicating that chronic exposure to low-level waterborne HBQs is associated with human bladder carcinogenesis.
基金
supported by grants from Alberta Innovates,the Canada Research Chairs(CRC)Program,and the Natural Sciences and Engineering Research Council of Canada(NSERC).Flow cytometry was performed at the University of Alberta’s Faculty of Medicine and Dentistry Flow Cytometry Facility,with additional support from the Faculty and the Canadian Foundation for Innovation(CFI).C.W.gratefully acknowledges financial support from the China Scholarship Council(CSC).
