Bastert G, Voelcker G, Peter G, Schmidt-Matthiesen H, Hohorst H J
Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 1976 Mar 19;85(3):299-307. doi: 10.1007/BF00284088.
The utility of 4-hydro-peroxy-cyclophosphamide for testing the selectivity of human tumours cells against cyclophosphamide in vitro was studied. 4-hydro-peroxy-cyclophosphamide in aqueous solution spontaneously decomposes to 4-hydroxy-cyclophosphamide, the primary product of metabolic activation of cyclophosphamide thus representing a new form of "activated" cyclophosphamide. From 31 human tumours including 21 mammarian-, 4 ovarial-, 2 uterine-carcinomas, 2 seminomas, 1 hypernephroma and 1 rectum-carcinoma cell suspensions were made and the effect on the 3H-Uridine- and the 3H-Thymidine-incorporation into the nucleic acids after short time incubation with the effect of 4-hydro-peroxy-cyclophosphamide and 4-hydroxy-cyclophosphamide. 7 malignomas showed high sensitivity both against 4-hydro-peroxy-cyclophosphamide and against 4-hydroxy-cyclophosphamide. No additional inhibitory effect of the peroxyde function besides of that of the alkylating moiety of the molecule was found. Accordingly 4-hydro-peroxy-cyclophosphamide because of its better availibility and stability may be used as "activated" cyclophosphamide in screening tests for cyclophosphamide-sensivity of human tumours in vitro.
研究了4-氢过氧环磷酰胺在体外测试人肿瘤细胞对环磷酰胺选择性方面的效用。4-氢过氧环磷酰胺在水溶液中会自发分解为4-羟基环磷酰胺,环磷酰胺代谢活化的主要产物因此代表了一种新形式的“活化”环磷酰胺。从31种人类肿瘤(包括21种乳腺癌、4种卵巢癌、2种子宫癌、2种精原细胞瘤、1种肾上腺瘤和1种直肠癌)制备了细胞悬液,并在与4-氢过氧环磷酰胺和4-羟基环磷酰胺作用短时间孵育后,观察其对3H-尿苷和3H-胸苷掺入核酸的影响。7种恶性肿瘤对4-氢过氧环磷酰胺和4-羟基环磷酰胺均表现出高敏感性。除了分子的烷基化部分的作用外,未发现过氧化物功能有额外的抑制作用。因此,由于其更好的可用性和稳定性,4-氢过氧环磷酰胺可在体外筛选人肿瘤对环磷酰胺敏感性的试验中用作“活化”环磷酰胺。