Sladek N E
J Pharmacol Exp Ther. 1977 May;201(2):518-26.
The cytotoxic action of certain antitumor agents is potentiated by centrophenoxine although centrophenoxine itself is not an antitumor agent. Previous investigations have suggested that centrophenoxine might potentiate the cytotoxicity produced by antitumor drugs that alkylate, and other modalities that damage, DNA, but that it would not potentiate the cytotoxicity produced by antitumor drugs that inflict cellular damage in other ways. To test this hypothesis, the antitumor effects of X-irradiation UV-irradiation, alkylating agents and antitumor drugs that are not ordinarily considered to be alkylating agents were determined in the presence and absence of centrophenoxine. Mouse P388 lymphoma cells growing in static suspension culture were used as the experimental tumor. The cytotoxic action of most alkylating agents was found to be potentiated by centrophenoxine; Included in this group were several difunctional nitrogen mustards, two ethylenimines, a nitrosourea and mitomycin C. Greatest enhancement, 7-fold, was of chlorambucil antitumor activity. Centrophenoxine did not potentiate the lethality of X- or UV-irradiation or the cytotoxicity of several antineoplastic drugs that are not alkylating agents.
尽管氯酯醒本身并非抗肿瘤药物，但某些抗肿瘤药物的细胞毒性作用会被氯酯醒增强。先前的研究表明，氯酯醒可能会增强通过烷基化作用的抗肿瘤药物以及其他损害DNA的方式所产生的细胞毒性，但不会增强通过其他方式造成细胞损伤的抗肿瘤药物所产生的细胞毒性。为了验证这一假设，在有和没有氯酯醒存在的情况下，测定了X射线照射、紫外线照射、烷基化剂以及通常不被认为是烷基化剂的抗肿瘤药物的抗肿瘤效果。在静态悬浮培养中生长的小鼠P388淋巴瘤细胞被用作实验肿瘤。发现大多数烷基化剂的细胞毒性作用被氯酯醒增强；这一组包括几种双功能氮芥、两种乙撑亚胺、一种亚硝基脲和丝裂霉素C。增强作用最大的是苯丁酸氮芥的抗肿瘤活性，增强了7倍。氯酯醒不会增强X射线或紫外线照射的致死性，也不会增强几种非烷基化抗肿瘤药物的细胞毒性。
