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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Arylamine N-Acetyltransferase, Bile Duct Neoplasms, Bile Ducts, Intrahepatic, Cell Line, Tumor, Cholangiocarcinoma, Epithelial Cells, Glutathione, Humans, Interferon-gamma, Interleukin-1beta, Isoenzymes, Nitric Oxide, Nitric Oxide Donors, Oxidation-Reduction, Oxidative Stress, RNA, Messenger, S-Nitrosoglutathione, Superoxides, Tumor Necrosis Factor-alpha.
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Do inflammatory cytokines suppress arylamine N-acetyltransferase 1 in cholangiocarcinoma cells? Context: 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. Human cholangiocarcinoma KKU-100 cells were treated with a mixture of proinflammatory cytokines (interferon-gamma, interleukin-1 beta and tumor necrosis factor-alpha) 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. 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.
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These findings indicate an association between inflammation and suppression of NAT1, which perhaps contributes to chemical-mediated toxicity and carcinogenesis. Final Decision: yes