effects of smoking and alcohol consumption on 5-fluorouracil‑related metabolic enzymes in oral squamous cell carcinoma

Yamashita,Tomomi; Kato,Keizo; Long,Nguyen  Khanh; Makita,Hiroki; Yonemoto,Kazuhiro; Iida,Kazuki; Tamaoki,Naritaka; Hatakeyama,Daijiro; Shibata,Toshiyuki

doi:10.3892/mco.2014.267

effects of smoking and alcohol consumption on 5-fluorouracil‑related metabolic enzymes in oral squamous cell carcinoma

Authors:
- Tomomi Yamashita
- Keizo Kato
- Nguyen Khanh Long
- Hiroki Makita
- Kazuhiro Yonemoto
- Kazuki Iida
- Naritaka Tamaoki
- Daijiro Hatakeyama
- Toshiyuki Shibata
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Affiliations: Department of Dentistry and Oral Surgery, Kouseiren Takaoka Hospital, Takaoka, Toyama 933-8555, Japan, Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Gifu University, Gifu, Gifu 501-1194, Japan
Published online on: March 7, 2014 https://doi.org/10.3892/mco.2014.267
Pages: 429-434

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Abstract

lifestyle, particularly smoking and alcohol consumption, may induce and/or inhibit drug metabolism. In order to reveal the effects of smoking and alcohol consumption on the 5-fluorouracil (5‑FU)‑related metabolic enzymes, namely thymidylate synthase, dihydropyrimidine dehydrogenase (DPD; a sole catabolic enzyme of 5-FU), orotate phosphoribosyl transferase (OPRT) and thymidine phosphorylase, in oral squamous cell carcinomas, the mRNA expression of these enzymes was investigated in 29 surgical specimens and compared by the Brinkman index and drinking years. The surgical specimens were divided into normal and tumor regions and were independently analyzed using quantitative reverse transcription‑polymerase chain reaction. There was a significantly positive correlation between DPD mRNA expression in these tissues and Brinkman index̸drinking years, with OPRT mRNA expression being significantly correlated to the Brinkman index in tumor tissues. These results revealed that lifestyle habits, including smoking and alcohol consumption, may vary the activity of the 5-FU‑related metabolic enzymes. DPD is the initial and rate‑limiting enzyme in the catabolic pathway of 5-FU. Therefore, smoking and alcohol consumption may reduce the anticancer activity of 5-FU, possibly through the induction of DPD activity.

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