Related Experiment Video
Updated: Jul 9, 2026
Induction of an Inflammatory Response in Primary Hepatocyte Cultures from Mice
Published on: March 10, 2017
Inflammatory cytokines promote inducible nitric oxide synthase-mediated DNA damage in hamster gallbladder epithelial
Amane Kitasato1, Yoshitsugu Tajima, Tamotsu Kuroki
1Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. a-kit@bg8.so-net.ne.jp
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-1beta, interferon-gamma, and tumor necrosis factor-alpha. 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.
