Double J A, Bibby M C, McCormick J E, McElhinney R S
School of Clinical Oncology, University of Bradford, West Yorkshire, UK.
Anticancer Drug Des. 1986 Apr;1(2):133-9.
Anti-tumour activity of a novel series of molecular combinations, seco-nucleosides where the carrier is a sugar-like fragment linking the pyrimidine anti-metabolite 5-fluorouracil (5-FU) with the alkylating agent N-chloroethyl-N-nitrosourea (CNU), is presented. Three tumour lines, from the mouse adenocarcinoma of the colon (MAC) series, with different sensitivities to 5-FU and CNU were employed. All four molecular combinations tested showed some activity in this system. B 3839, in which 5-FU is linked by a SC--N bond, showed greatest activity against the ascitic tumour MAC 15A but was inactive at non-toxic doses against the solid tumour MAC 13. Activity against MAC 15A was of the same order as that achieved with 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea. In contrast B 3958, with an OC--N bond, proved inactive against the ascitic tumour but was highly active against MAC 13. The factors responsible for this reversal are as yet unknown.
本文介绍了一系列新型分子组合的抗肿瘤活性，这些分子组合为裂环核苷，其载体是一种类似糖的片段，将嘧啶抗代谢物5-氟尿嘧啶（5-FU）与烷化剂N-氯乙基-N-亚硝基脲（CNU）连接起来。使用了来自小鼠结肠腺癌（MAC）系列的三种肿瘤细胞系，它们对5-FU和CNU具有不同的敏感性。所测试的所有四种分子组合在该系统中均显示出一定活性。其中5-FU通过SC-N键连接的B 3839对腹水型肿瘤MAC 15A显示出最大活性，但在无毒剂量下对实体瘤MAC 13无活性。对MAC 15A的活性与1-(2-氯乙基)-3-(4-甲基环己基)-1-亚硝基脲所达到的活性相当。相比之下，具有OC-N键的B 3958对腹水型肿瘤无活性，但对MAC 13具有高活性。造成这种逆转的因素尚不清楚。
