Gurtoo H L, Gessner T, Culliton P
Cancer Treat Rep. 1976 Sep;60(9):1285-94.
The effects of low and high doses of three anticancer agents, cyclophosphamide, vincristine, and prednisone (given individually or in various combinations), on oxidative and conjugation pathways were studied in Sprague-Dawley male rats. Cyclophosphamide used alone at low doses decreased aniline hydroxylase and ethylmorphine demethylase activities by about 20% and at high doses produced a 30%-50% decrease in the specific activities of several microsomal mixed-function oxygenase activities, in the contents of cytochromes P-450 and b5, and in the magnitudes of type I and II drug-binding spectrum. The levels of microsomal glucouronidase, glucuronyl transferase, and sulfatase per gram of liver were also decreased (30%-50%) by the high dose of cyclophosphamide. The high dose of cyclophosphamide in conjunction with either vincristine or prednisone also produced a noticeable decrease in several activities tested; however, when cyclophosphamide was given at either low or high doses in combination with vincristine and prednisone, the activities tested were comparable to those seen in untreated controls. The mechanism of this protection is presently unknown. Vincristine, at both low and high doses, produced little effect on oxidative pathways; however, at low doses it caused a significant increase (80%) in the specific activity of hepatic microsomal sulfatase. This effect was also discernible when vincristine was given in combination with cyclophosphamide and prednisone. Other than producing a 15% decrease in liver weight and a 40% decrease in the specific activity of microsomal glucuronidase, the high dose of prednisone used had no effect on various activities tested. Results of these studies indicate a potential for drug interaction among anticancer agents and supportive drugs used in combination cancer chemotherapy.
研究了低剂量和高剂量的三种抗癌药物环磷酰胺、长春新碱和泼尼松（单独给药或多种组合给药）对Sprague-Dawley雄性大鼠氧化和结合途径的影响。低剂量单独使用环磷酰胺使苯胺羟化酶和乙基吗啡脱甲基酶活性降低约20%，高剂量则使几种微粒体混合功能氧化酶活性的比活性、细胞色素P-450和b5的含量以及I型和II型药物结合光谱的强度降低30%-50%。高剂量环磷酰胺还使每克肝脏中微粒体葡萄糖醛酸酶、葡萄糖醛酸转移酶和硫酸酯酶的水平降低（30%-50%）。高剂量环磷酰胺与长春新碱或泼尼松联合使用也使所测试的几种活性显著降低；然而，当环磷酰胺低剂量或高剂量与长春新碱和泼尼松联合使用时，所测试的活性与未处理对照组相当。这种保护机制目前尚不清楚。长春新碱无论低剂量还是高剂量对氧化途径影响都很小；然而，低剂量时它使肝脏微粒体硫酸酯酶的比活性显著增加（80%）。当长春新碱与环磷酰胺和泼尼松联合使用时，这种作用也很明显。高剂量泼尼松除了使肝脏重量减轻15%和微粒体葡萄糖醛酸酶的比活性降低40%外，对所测试的各种活性没有影响。这些研究结果表明，联合癌症化疗中使用的抗癌药物和支持性药物之间存在药物相互作用的可能性。
