Kim J H, Alfieri A A, Kim S H, Young C W
Cancer Res. 1986 Mar;46(3):1120-3.
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.
氯尼达明是一种有效的精子发生抑制剂和热增敏剂。氯尼达明已确定的主要生化作用位点是对能量代谢的选择性抑制作用，这一作用既体现在生殖细胞线粒体中与NAD相关的反应中，也体现在通过抑制线粒体结合型己糖激酶对多种肿瘤细胞系的糖酵解代谢的抑制作用上。我们进行了体内肿瘤实验，以确定氯尼达明与辐射联合使用时是否能增强辐射对两种小鼠肿瘤的细胞毒性作用。评估了单次急性给予氯尼达明（100 mg/kg）和单次X射线照射对BALB/c小鼠移植的甲基胆蒽诱导的纤维肉瘤以及C3H/He小鼠辐射诱导的纤维肉瘤的联合效应。当在X射线照射之前或之后立即给予氯尼达明时，其放射增敏作用最大。氯尼达明对甲基胆蒽诱导的纤维肉瘤肿瘤的剂量修正因子估计为1.36，对辐射诱导的纤维肉瘤肿瘤为1.25。联合治疗后皮肤反应没有不成比例地增强。辐射增效作用的当前结果可能部分归因于细胞培养研究的结果，即氯尼达明是潜在致死性损伤修复的有效抑制剂。
