Look M P, Musch E
Department of Internal Medicine, University of Bonn, FRG.
Chemotherapy. 1994 Jan-Feb;40(1):8-15. doi: 10.1159/000239163.
There is evidence that a variety of anticancer drugs exert their cytotoxic activity by a free-radical-mediated mechanism. These drugs include anthracyclines such as adriamycin, daunorubicin, 4-epi-adriblastin as well as bleomycin, procarbazine, vincristin, cyclophosphamide, etoposide and mitomycin C. The aim of this study was to investigate whether cancer patients who underwent polychemotherapy (n = 44) show more signs of oxidative stress in plasma than a group of healthy controls (n = 52). As an index of free radical generation, plasma concentrations of thiobarbituric-acid-reactive substances (TBARS), well-accepted as markers for oxidative stress, were determined by fluorometric detection after separation by high-performance liquid chromatography. In 12 cases, the TBARS were measured both before and after a chemotherapy course. After chemotherapy, 10 of 12 patients showed a marked increase in plasma TBARS concentration compared to values measured before therapy [9.02 +/- 1.84 nmol/ml (n = 12) vs. 11.58 +/- 2.49 nmol/ml (n = 12); p = 0.002, t-test for paired observations]. Tumor patients in general had significantly larger amounts of TBARS in plasma in comparison with a control group [mean 11.88 +/- 3.51 nmol/ml (n = 44) vs. 7.51 +/- 2.14 nmol/ml (n = 52); p < 0.001, t test]. Our results are evidence that repetitive polychemotherapy with radical-generating compounds may exceed the antioxidative capacities of cancer patients and may lead to oxidative stress.
有证据表明,多种抗癌药物通过自由基介导机制发挥其细胞毒性活性。这些药物包括蒽环类药物,如阿霉素、柔红霉素、4-表阿霉素,以及博来霉素、丙卡巴肼、长春新碱、环磷酰胺、依托泊苷和丝裂霉素C。本研究的目的是调查接受多药化疗的癌症患者(n = 44)与一组健康对照者(n = 52)相比,血浆中是否表现出更多氧化应激迹象。作为自由基生成的指标,硫代巴比妥酸反应性物质(TBARS)的血浆浓度通过高效液相色谱分离后的荧光检测来测定,TBARS是公认的氧化应激标志物。在12例患者中,在一个化疗疗程前后均测量了TBARS。化疗后,12例患者中有10例血浆TBARS浓度与治疗前相比显著升高[9.02±1.84 nmol/ml(n = 12)对11.58±2.49 nmol/ml(n = 12);p = 0.002,配对观察t检验]。总体而言,肿瘤患者血浆中的TBARS含量与对照组相比显著更高[平均值11.88±3.51 nmol/ml(n = 44)对7.51±2.14 nmol/ml(n = 52);p < 0.001,t检验]。我们的结果证明,使用产生自由基的化合物进行重复多药化疗可能会超过癌症患者的抗氧化能力,并可能导致氧化应激。