ABSTRACT
Clonorchis sinensis is one of the most prevalent parasitic helminths in Korea. Although cholangiocarcinoma can be induced by C. sinensis infection, the underlying mechanism is not clearly understood. To assess the role of C. sinensis infection in carcinogenesis, an in vitro system was established using the human epithelial cell line HEK293T. In cells exposed to the excretory/secretory products (ESP) of C. sinensis and the carcinogen dimethylnitrosamine (DMN), cellular proliferation and the proportion of cells in the G2/M phase increased. Moreover, the expression of the cell cycle proteins E2F1, p-pRb, and cyclin B was dramatically increased when ESP and DMN were added together. Similarly, the transcription factor E2F1 showed its highest level of activity when ESP and DMN were added simultaneously. These findings indicate that DMN and ESP synergistically affect the regulation of cell cycle-related proteins. Our results suggest that exposure to C. sinensis and a small amount of a carcinogen such as DMN can promote carcinogenesis in the bile duct epithelium via uncontrolled cellular proliferation and the upregulation of cell cycle-related proteins.
Subject(s)
Animals , Humans , Carcinogens/metabolism , Cell Cycle/drug effects , Cell Line , Cell Proliferation , Clonorchis sinensis/metabolism , Dimethylnitrosamine/toxicity , Epithelial Cells/drug effectsABSTRACT
Protective effects of metallothionein (MT) have been studied against dimethylnitosamine (DMN) toxicity in laboratory rats. MT was induced by feeding rats on repeated sublethal doses of cadmium and zinc. These rats were subsequently administered DMN. Methemoglobin and nitric oxides, the established markers of DMN toxicity, were estimated in the blood samples of MT protected rats. Preinduction of MT decreased methemoglobin and ameliorated the generation of nitric oxides. Antioxidative effects of MT may have manifested these results, however, an effect on N-nitrosation is also speculated.