Korean J Parasitol.  2008 Sep;46(3):127-132. 10.3347/kjp.2008.46.3.127.

Effects of Excretory/Secretory Products from Clonorchis sinensis and the Carcinogen Dimethylnitrosamine on the Proliferation and Cell Cycle Modulation of Human Epithelial HEK293T Cells

• Kim EM
• Kim JS
• Choi MH
• Hong ST
• Bae YM

• KMID: 1720554
• DOI: http://doi.org/10.3347/kjp.2008.46.3.127

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.

Keyword

Clonorchis sinensis; cell cycle; excretory/secretory products; carcinogenesis; dimethylnitrosamine

MeSH Terms

Animals
Carcinogens/*metabolism/*toxicity
Cell Cycle/drug effects
Cell Line
Cell Proliferation
Clonorchis sinensis/*metabolism
Dimethylnitrosamine/*toxicity
Epithelial Cells/*drug effects
Humans