Modulation of intracellular glutathione concentration alters dehydropyrimidine dehydrogenase activity in peripheral blood mononuclear cells

被引:4
|
作者
Iwata, S
Takabayashi, A
Yamaoka, Y
机构
[1] Kyoto City Hosp, Dept Surg, Nakagyo Ku, Kyoto 6048845, Japan
[2] Kitano Hosp, Tazuke Kohukai Med Res Inst, Dept Gastroenterol Surg & Oncol, Kita Ku, Osaka 5308480, Japan
[3] Kyoto Univ, Grad Sch Med, Dept Surg Gastroenterol, Sakyo Ku, Kyoto 6068507, Japan
关键词
dehydropyrimidine dehydrogenase; 5-fluorouracil; glutathione; peripheral blood mononuclear cells; side effects;
D O I
10.1007/s102380200013
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Dehydropyrimidine dehydrogenase (DPD) is the initial key enzyme in the regulation of 5-fluorouracil catabolism and thus controls availability of 5-fluorouracil for anabolism. Modulation of DPD activity may increase the antitumor effect and avoid toxic side effects in 5-fluorouracil-based chemotherapy. We measured DPD activity in peripheral blood mononuclear cells from cancer patients and simultaneously monitored intracellular glutathione (GSH) and plasma GSH levels. There was a significant linear relationship between DPD activity and intracellular GSH levels in peripheral blood mononuclear cells obtained from cancer patients. Suppression of intracellular GSH level by buthionine sulfoximine decreased DPD activity, while enhancement of intracellular GSH level by 2-mercaptoethanol increased DPD activity. This study indicated that alteration of intracellular GSH concentration may modulate DPD activity.
引用
收藏
页码:99 / 103
页数:5
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