Activation of 5'-deoxy-5-fluorouridine by thymidine phosphorylase in human tumors.
Activation of 5'-deoxy-5-fluorouridine by thymidine phosphorylase in human tumors.
复制标题
人类肿瘤中胸苷磷酸化酶激活 5-脱氧-5-氟尿苷。
DOI：
10.1248/cpb.31.175
复制
发表时间：
1983
影响因子：
1.7
通讯作者：
Hideo Ishitsuka
中科院分区：
文献类型：
--
作者：
Akira Kono;Yasuhiro Hara;S. Sugata;Y. Karube;Yoshikazu Matsushima;Hideo Ishitsuka
以胸苷（dThd）、尿苷（Urd）和5 ′-脱氧-5-氟尿苷（5 ′-DFUR）为底物，测定了人肿瘤、相同器官的正常组织和小鼠（Sarcoma-180）及豚鼠（Line-10）肿瘤提取物中嘧啶核苷磷酸化酶的活性。人肿瘤组织提取物的核苷裂解活性高于同一器官的正常组织提取物。在人体组织中，对dThd的磷酸化活性高，而对Urd的磷酸化活性低。在动物肿瘤中，Urd是最好的底物。1-（2 ′-脱氧-β-D-吡喃葡萄糖基）-胸腺嘧啶（GPT）是尿苷磷酸化酶的特异性抑制剂，它能抑制动物肿瘤提取物中Urd和5 ′-DFUR的磷酸化，但不能抑制人肿瘤提取物中dThd和5 ′-DFUR的磷酸化。从人肺癌组织中部分纯化了胸苷磷酸化酶。对dThd和5 '-DFUR的Km值分别为2.43×10-4 M和1.69×10-3 M。我们的结论是，在人类肿瘤中，胸苷磷酸化酶活性将5 '-DFUR转化为5-氟尿嘧啶，一种活化形式。
Activities of pyrimidine nucleoside phosphorylases were assayed in extracts of human tumors, normal tissues of the same organs and tumors of mice (Sarcoma-180) and guinea pigs (Line-10), with thymidine (dThd), uridine (Urd), and 5'-deoxy-5-fluorouridine (5'-DFUR) as substrates. The nucleoside cleaving activities were higher in extracts of human tumor tissues than in those of normal tissues of the same organs. In human tissues, phosphorolytic activitiy towards dThd was high, while that towards Urd was low. In animal tumors, Urd was the best substrate. 1-(2'-Deoxy-β-D-glucopyranosyl)-thymine (GPT), a specific inhibitor of uridine phosphorylase, inhibited the phosphorolysis of Urd and 5'-DFUR in extracts of animal tumors, but not that of dThd and 5'-DFUR in extracts of human tumors. A thymidine phosphorylase preparation was partialy purified from human lung cancer. Km values of the preparation were 2.43×10-4 M and 1.69×10-3 M for dThd and 5'-DFUR, respectively. We conclude that in human tumors a thymidine phosphorylase activity converts 5'-DFUR to 5-fluorouracil, an activated form.