Studies on the mechanism of action of 5‐aziridinyl‐2,4‐dinitrobenzamide (CB 1954), a selective inhibitor of the walker tumour
Studies on the mechanism of action of 5‐aziridinyl‐2,4‐dinitrobenzamide (CB 1954), a selective inhibitor of the walker tumour
复制标题
Walker 肿瘤选择性抑制剂 5-氮丙啶基-2,4-二硝基苯甲酰胺 (CB 1954) 作用机制的研究
DOI：
10.1002/ijc.2910070110
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发表时间：
1971
影响因子：
6.4
通讯作者：
D. Melzack
中科院分区：
文献类型：
--
作者：
T. Connors;D. Melzack
CB 1954是一种单功能烷化剂，对步行者癌具有特殊的活性，但对许多其他动物肿瘤无活性。对CB 1954具有获得性耐药性的步行者肿瘤系对美法仑具有交叉耐药性，这意味着共同的作用机制，尽管其他对美法仑高度敏感的肿瘤不受CB 1954的影响。CB 1954对DNA和RNA合成的影响也与美法仑相似。未观察到CB 1954与肿瘤细胞DNA的结合与其敏感性之间的相关性。当与美法仑和CB 1954孵育时，步行者肿瘤反应的差异表明，后者可能具有抗代谢物的某些特征。在初步实验中，其对步行者癌的选择性抗肿瘤作用已被嘌呤生物合成中的中间体完全逆转。
CB 1954, a monofunctional alkylating agent, has exceptional activity against the Walker carcinoma yet is inactive against a large number of other animal tumours. A line of the Walker tumour with acquired resistance to CB 1954 was cross‐resistant to Melphalan, implying a common mechanism of action, although other tumours highly sensitive to Melphalan were not affected by CB 1954. CB 1954 was also similar to Melphalan in its effects on DNA and RNA synthesis. No correlation was observed between binding of CB 1954 to the DNA of tumour cells and their sensitivity to it. Differences in response of the Walker tumour when incubated with Melphalan and CB 1954 suggest that the latter agent may have some features of an anti‐metabolite. In preliminary experiments, its selective anti‐tumour effect against the Walker carcinoma has been completely reversed by an intermediate in purine biosynthesis.