Lelieveld P, van Putten L M
Cancer Treat Rep. 1976 Apr;60(4):373-9.
The biologic activity in terms of survival of normal hematopoietic stem, osteosarcoma, and L1210 leukemia cells was determined for the following compounds:cyclophosphamide, its derivatives isophosphamide and trophosphamide, its possible metabolites nor-nitrogen mustard, hydroxylamine mustard, 4-ketocyclophosphamide, and and acrolein, and two substitutes for its primary active metabolite 4-hydroxycyclosphamide anhydro-dimer (4-hydroxy-CP-anhydro-dimer) and 4-hydroperoxycyclophosphamide (4-hydroperoxy-CP). On a molar basis none of the compounds shows a better therapeutic ratio between osteosarcoma and bone marrow stem cells than the parent compound. The therapeutic ratio between L1210 leukemia and normal cells is slightly better for 4-hydroperoxy-CP only. It may be concluded that the conversion of 4-hydroxy-CP-anhydro-dimer and 4-hydroperoxy-CP to the primary active metabolite 4-hydroxycyclophosphamide differs quantitatively. Moreover, it appears that by the use of these precursors a better therapeutic ratio might be obtained for some malignancies but not for others.
测定了以下化合物对正常造血干细胞、骨肉瘤细胞和L1210白血病细胞的生存生物活性：环磷酰胺、其衍生物异环磷酰胺和曲磷酰胺、其可能的代谢产物去甲氮芥、羟胺氮芥、4-酮环磷酰胺、丙烯醛，以及其主要活性代谢产物4-羟基环磷酰胺脱水二聚体（4-羟基-CP-脱水二聚体）和4-氢过氧环磷酰胺（4-氢过氧-CP）的两种替代物。在摩尔基础上，没有一种化合物在骨肉瘤和骨髓干细胞之间显示出比母体化合物更好的治疗指数。仅4-氢过氧-CP在L1210白血病和正常细胞之间的治疗指数略高。可以得出结论，4-羟基-CP-脱水二聚体和4-氢过氧-CP向主要活性代谢产物4-羟基环磷酰胺的转化在数量上有所不同。此外，似乎通过使用这些前体，对于某些恶性肿瘤可能会获得更好的治疗指数，但对其他恶性肿瘤则不然。
