Robertson N, Haigh A, Adams G E, Stratford I J
MRC Radiobiology Unit, Chilton, Didcot, U.K.
Eur J Cancer. 1994;30A(7):1013-9. doi: 10.1016/0959-8049(94)90134-1.
Twenty-three human tumour cell lines (lung, breast, and colon) and eight rodent cell lines were evaluated for their sensitivity to the quinone-based anticancer drug EO9 [3-hydroxymethyl-5-aziridinyl-1-methyl-2-(1H indole-4,7-dione)prop-beta-en-alpha-o1]. Sensitivity was compared with the intracellular levels of DT-diaphorase, and cell lines showing highest enzyme activity tended to be the most sensitive to EO9. The role of DT-diaphorase in determining drug sensitivity was confirmed by using the enzyme inhibitor dicoumarol, which protects cells containing high levels of DT-diaphorase from the cytotoxic action of EO9. Hypoxia increased the cytotoxicity of cells containing low but not high levels of DT-diaphorase, implying that both 1- and 2-electron reductive activation processes can be important for expression of EO9 toxicity. It is concluded that EO9 is a potentially useful agent in the enzyme directed approach to the use of bioreductive drugs in cancer therapy.
对23种人类肿瘤细胞系（肺癌、乳腺癌和结肠癌）和8种啮齿动物细胞系进行了评估，以确定它们对基于醌的抗癌药物EO9 [3 - 羟甲基 - 5 - 氮丙啶基 - 1 - 甲基 - 2 - (1H - 吲哚 - 4,7 - 二酮)丙 - β - 烯 - α - 醇] 的敏感性。将敏感性与细胞内DT - 黄递酶的水平进行比较，显示最高酶活性的细胞系往往对EO9最敏感。通过使用酶抑制剂双香豆素证实了DT - 黄递酶在确定药物敏感性中的作用，双香豆素可保护含有高水平DT - 黄递酶的细胞免受EO9的细胞毒性作用。缺氧增加了含有低水平而非高水平DT - 黄递酶的细胞的细胞毒性，这意味着单电子和双电子还原激活过程对于EO9毒性的表达都可能很重要。得出的结论是，在癌症治疗中使用生物还原药物的酶导向方法中，EO9是一种潜在有用的药物。
