对阿糖胞苷、胸苷和6-甲基巯基嘌呤核苷耐药的人T淋巴母细胞中的核苷转运与阿糖胞苷（araC）代谢

Nucleoside transport and cytosine arabinoside (araC) metabolism in human T lymphoblasts resistant to araC, thymidine and 6-methylmercaptopurine riboside.

作者信息

Young I, Young G J, Wiley J S, van der Weyden M B

出版信息

Eur J Cancer Clin Oncol. 1985 Sep;21(9):1077-82. doi: 10.1016/0277-5379(85)90294-9.

Abstract

Alteration in cellular nucleoside transport characteristics, deoxynucleoside triphosphate (dNTP) pools and araCTP formation from cytosine arabinoside (araC) were determined for human T lymphoblasts (CCRF-CEM) resistant to araC, thymidine or 6-methylmercaptopurine riboside (6-MMPR). AraC resistance was accompanied by reduced activities of deoxycytidine and thymidine kinases, lowered cellular deoxycytidine triphosphate concentration and markedly reduced formation of araCTP from araC. The ID50 values for araC, araCTP formation and dNTP levels of thymidine-resistant lymphoblasts, which exhibited reduced thymidine kinase activity, and 6-MMPR-resistant cells, with reduced adenosine kinase activity, were similar to the corresponding parameters of wild type lymphoblasts. The nucleoside transport sites density determined by nitrobenzylmercaptopurine riboside binding was comparable for araC-resistant, wild type and thymidine- or 6-MMPR-resistant lymphoblasts.

摘要

对人T淋巴母细胞（CCRF-CEM）对阿糖胞苷、胸苷或6-甲基巯基嘌呤核苷（6-MMPR）耐药的细胞核苷转运特性、脱氧核苷三磷酸（dNTP）池以及由阿糖胞苷（araC）形成阿糖胞苷三磷酸（araCTP）的情况进行了测定。阿糖胞苷耐药伴随着脱氧胞苷激酶和胸苷激酶活性降低、细胞内脱氧胞苷三磷酸浓度降低以及由阿糖胞苷形成阿糖胞苷三磷酸的显著减少。胸苷耐药的淋巴母细胞（其胸苷激酶活性降低）和6-MMPR耐药细胞（其腺苷激酶活性降低）对阿糖胞苷的ID50值、阿糖胞苷三磷酸形成和dNTP水平与野生型淋巴母细胞的相应参数相似。通过硝基苄基巯基嘌呤核苷结合测定的核苷转运位点密度，对于阿糖胞苷耐药、野生型以及胸苷或6-MMPR耐药的淋巴母细胞来说是相当的。