Rapid Communication
Copyright ©2007 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2007; 13(46): 6219-6225
Published online Dec 14, 2007. doi: 10.3748/wjg.v13.i46.6219
Inflammatory cytokines suppress arylamine N-acetyltransferase 1 in cholangiocarcinoma cells
Benjaporn Buranrat, Auemduan Prawan, Banchob Sripa, Veerapol Kukongviriyapan
Benjaporn Buranrat, Auemduan Prawan, Veerapol Kukongviriyapan, Department of Pharmacology, Faculty of Medicine, Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen 40002, Thailand
Banchob Sripa, Department of Pathology, Faculty of Medicine, Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University, Khon Kaen 40002, Thailand
Author contributions: All authors contributed equally to the work.
Supported by Khon Kaen University Research Fund, Grant from National Science and Technology Development Agency through the Research-Team-Strenghtening Grant Scheme 2006
Correspondence to: Veerapol Kukongviriyapan, Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand. veerapol@kku.ac.th
Telephone: +66-43-348397 Fax: +66-43-348397
Received: July 25, 2007
Revised: September 14, 2007
Accepted: October 27, 2007
Published online: December 14, 2007
Abstract

AIM: To evaluate the effect of inflammatory cytokines on arylamine N-acetyltransferase 1 (NAT1), which is a phase-II enzyme involved in the biotransformation of aromatic and heterocyclic amines found in food, drugs and the environment.

METHODS: Human cholangiocarcinoma KKU-100 cells were treated with a mixture of proinflammatory cytokines (interferon-γ, interleukin-1β, and tumor necrosis factor-α) for 48 h, and the effect on NAT1 activity was assessed by high performance liquid chromatography, while NAT1 expression was determined by reverse-transcription polymerase chain reaction. The oxidative stress on the cells was examined by the formation of nitric oxide, superoxide anion and glutathione (GSH) levels. The cells were also treated with S-nitroso-glutathione (GSNO), a nitric oxide donor, to see if the responses were similar to those obtained with the inflammatory cytokines.

RESULTS: Cytokines suppressed NAT1 activity, reducing the Vmax without affecting the Km. Cytokines also had a significant impact on the induction of nitric oxide production and in reducing the redox ratios of glutathione (GSH) and GSH disulfide. Treatment with GSNO for 2-48 h reduced NAT1 activity without affecting the GSH ratio. Moreover, inflammatory cytokines and GSNO suppressed NAT1 mRNA expression.

CONCLUSION: These findings indicate an association between inflammation and suppression of NAT1, which perhaps contributes to chemical-mediated toxicity and carcinogenesis.

Keywords: Arylamine N-acetyltransferase 1; Phase II drug-metabolizing enzyme; Inflammatory cytokine; Oxidative stress; Cholangiocarcinoma