Potentiation of radiation effects on two murine tumors by lonidamine.
Potentiation of radiation effects on two murine tumors by lonidamine.
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发表时间：
1986-03
期刊：
影响因子：
11.2
通讯作者：
J. Kim;A. Alfieri;S. Kim;C. Young
中科院分区：
文献类型：
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作者：
J. Kim;A. Alfieri;S. Kim;C. Young
氯尼达明是一种有效的精子发生抑制剂和高热增敏剂。氯尼达明生化作用的主要确定位点是选择性抑制生殖细胞线粒体中NAD-连接反应中的能量代谢，以及通过抑制细胞内结合的己糖激酶抑制多种肿瘤细胞系的糖酵解代谢。我们进行了体内肿瘤实验，以确定是否氯尼达明时，结合放射线可以加强细胞毒性效应的放射对两个小鼠肿瘤。本文观察了氯尼达明（100 mg/kg）单次急性给药和X射线单次照射对BALB/c小鼠甲基胆蒽（methylcholanthrene）移植性纤维肉瘤和C_3 H/He小鼠放射性纤维肉瘤的联合作用。当氯尼达明在X射线照射前或照射后立即给药时，氯尼达明的放射增敏作用最大。氯尼达明的剂量修正因子估计为1.36甲基胆蒽诱导的纤维肉瘤肿瘤和1.25辐射诱导的纤维肉瘤肿瘤。在联合治疗后，没有不成比例的皮肤反应增强。辐射增强效应的目前结果可能部分归因于细胞培养研究的发现，即氯尼达明是潜在致死性损伤修复的有效抑制剂。
Lonidamine is a potent inhibitor of spermatogenesis and a hyperthermic sensitizer. The principal established locus of biochemical action of lonidamine is a selective inhibitory effect of the energy metabolism either in NAD-linked reactions in germ cell mitochondria, as well as the glycolytic metabolism of a variety of tumor cell lines by means of inhibition of mitochondrially bound hexokinase. We carried out in vivo tumor experiments to determine whether lonidamine when combined with radiation could potentiate the cytotoxic effects of radiation on two murine tumors. The combined effects of single acute lonidamine (100 mg/kg) and single dose X-irradiation were evaluated on the transplanted methylcholanthrene-induced fibrosarcoma in BALB/c mice and on the radiation-induced fibrosarcoma in C3H/He mice. The radiosensitizing effect by lonidamine was maximal when lonidamine was administered immediately prior to or after X-irradiation. The dose modifying factor of lonidamine is estimated to be 1.36 for methylcholanthrene-induced fibrosarcoma tumors and 1.25 for radiation-induced fibrosarcoma tumors. There was no disproportionately enhanced skin reaction following the combined treatments. The present results of the potentiating effects of radiation may be attributed, in part, to the findings of cell culture studies that lonidamine is a potent inhibitor of repair of potentially lethal damage.