Katsumata Kenji, Tomioka Hidenori, Sumi Tetsuo, Yamashita Shinya, Takagi Makoto, Kato Fumiaki, Nakamura Ryuji, Koyanagi Yasuhisa, Aoki Tatsuya, Kato Kohichiro
Department of Digestive Tract Surgery, Hachioji Medical Center, Tokyo Medical University, 1163, Tate-machi, Hachioji, Tokyo, 193-0944, Japan.
Cancer Chemother Pharmacol. 2003 Feb;51(2):155-60. doi: 10.1007/s00280-002-0526-3. Epub 2003 Jan 15.
Using tumor tissue specimens from colon carcinoma patients given 5-fluorouracil (5-FU) by two different administration methods, we investigated the degree of correlation between clinicopathologic factors and the kinetics of metabolic enzymes for 5-FU.
Group A patients received 500 mg/day of 5-FU as a rapid infusion over 2 h for 3 days preoperatively, and group B patients received 500 mg/day of 5-FU as a continuous infusion for 3 days preoperatively. The activities of orotate phosphoribosyl transferase (OPRT), thymidine phosphorylase (TP), uridine phosphorylase (UP), and dihydropyrimidine dehydrogenase (DPD) were measured by separation on ion-exchange filter paper, by high-performance liquid chromatography (HPLC) with UV detection and by HPLC with radioactive flow monitoring, respectively, and the [(3)H]-5-fluorodeoxyuridine monophosphate binding site in thymidylate synthetase (TS) was determined as an index of the amount of TS using a radiobinding assay. The TS inhibition rate (TSIR) was calculated from the formula: 1-(TS(free)/TS(total))x100. Finally, 5-FU incorporation into RNA (FRNA) was measured by capillary gas chromatography-mass spectrometry.
In group A patients, FRNA showed a positive correlation only with OPRT, and TSIR showed positive correlations with OPRT and TP, but a negative correlation with TS. In group B patients, FRNA showed a negative correlation with DPD, and TSIR showed a negative correlation with TS. No difference in TSIR levels was seen between groups A and B. FRNA was higher in group A than in group B, but the difference was not statistically significant.
The method of administration may influence 5-FU metabolism in colon carcinoma patients.
通过对采用两种不同给药方法给予5-氟尿嘧啶（5-FU）的结肠癌患者的肿瘤组织标本进行研究，我们调查了临床病理因素与5-FU代谢酶动力学之间的相关程度。
A组患者在术前3天每天接受500mg 5-FU，于2小时内快速输注，B组患者在术前3天每天接受500mg 5-FU，持续输注。分别通过离子交换滤纸分离、带紫外检测的高效液相色谱法（HPLC）以及带放射性流动监测的HPLC来测定乳清酸磷酸核糖基转移酶（OPRT）、胸苷磷酸化酶（TP）、尿苷磷酸化酶（UP）和二氢嘧啶脱氢酶（DPD）的活性，并使用放射结合测定法将胸苷酸合成酶（TS）中的[(3)H]-5-氟脱氧尿苷单磷酸结合位点确定为TS量的指标。TS抑制率（TSIR）根据公式计算：1 - (TS(游离)/TS(总量))×100。最后，通过毛细管气相色谱-质谱法测定5-FU掺入RNA（FRNA）的情况。
在A组患者中，FRNA仅与OPRT呈正相关，TSIR与OPRT和TP呈正相关，但与TS呈负相关。在B组患者中，FRNA与DPD呈负相关，TSIR与TS呈负相关。A组和B组之间TSIR水平未见差异。A组的FRNA高于B组，但差异无统计学意义。
给药方法可能会影响结肠癌患者的5-FU代谢。
