摘要
AIM: To investigate the link between chronic biliary inflammation and carcinogenesis using hamster gallbladder epithelial cells. METHODS: Gallbladder epithelial cells were isolated from hamsters and cultured with a mixture of inflammatory cytokines including interleukin-1β,interferon-γ,and tumor necrosis factor-α. Inducible nitric oxide synthase (iNOS) expression,nitric oxide (NO) generation,and DNA damage were evaluated. RESULTS: NO generation was increased significantly following cytokine stimulation,and suppressed by an iNOS inhibitor. iNOS mRNA expression was demonstrated in the gallbladder epithelial cells during exposure to inflammatory cytokines. Furthermore,NO-dependent DNA damage,estimated by the comet assay,was significantly increased by cytokines,and decreased to control levels by an iNOS inhibitor. CONCLUSION: Cytokine stimulation induced iNOS expression and NO generation in normal hamster gallbladder epithelial cells,which was sufficient to cause DNA damage. These results indicate that NO-mediated genotoxicity induced by inflammatory cytokines through activation of iNOS may be involved in the process of biliary carcinogenesis in response to chronic inflammation of the biliary tree.
AIM： To investigate the link between chronic biliary inflammation and carcinogenesis using hamster gallbladder epithelial cells.METHODS： Gallbladder epithelial cells were isolated from hamsters and cultured with a mixture of inflammatory cytokines including interleukin-1β, interferon-γ, and tumor necrosis factor-α. Inducible nitric oxide synthase （iNOS） expression, nitric oxide （NO） generation, and DNA damage were evaluated.RESULTS： NO generation was increased significantly following cytokine stimulation, and suppressed by an iNOS inhibitor, iNOS mRNA expression was demonstrated in the gallbladder epithelial cells during exposure to inflammatory cytokines. Furthermore, NO-dependent DNA damage, estimated by the comet assay, was significantly increased by cytokines, and decreased to control levels by an iNOS inhibitor.CONCLUSION： Cytokine stimulation induced iNOS expression and NO generation in normal hamster gallbladder epithelial cells, which was sufficient to cause DNA damage. These results indicate that NO-mediated genotoxicity induced by inflammatory cytokines through activation of iNOS may be involved in the process of biliary carcinogenesis in response to chronic inflammation of the biliary tree.
