Inflammatory Cytokines Promote Inducible Nitric Oxide Synthase-mediated DNA Damage in Hamster Gallbladder Epithelial Cells

Overview

Journal World J Gastroenterol

Publisher Baishideng Publishing Group

Specialty Gastroenterology

Date 2007 Dec 18

PMID 18081227

Citations 8

Authors

Amane Kitasato

Yoshitsugu Tajima

Tamotsu Kuroki

Ryuji Tsutsumi

Tomohiko Adachi

Takehiro Mishima

Takashi Kanematsu

Affiliations

Soon will be listed here.

Abstract

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.

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