Gajewska J, Szczypka M, Izbicki T, Klepacka T, Laskowska-Klita T
Department of Biochemistry, National Research Institute of Mother and Child, Warsaw, Poland.
J Cancer Res Clin Oncol. 1996;122(8):483-8. doi: 10.1007/BF01187160.
The present study demonstrates the activities of antioxidant and glutathione-associated enzymes and the level of glutathione in Wilms' tumour (nephroblastoma) samples after chemotherapy (mainly actinomycin D and vincristine). We observed higher activity of superoxide dismutase in Wilms' tumour compared to adjacent morphologically unchanged kidney. On the other hand, in this tumour lower activities of catalase and the glutathione-associated enzymes glutathione synthetase, gamma-glutamyl transpeptidase, glutathione reductase and total glutathione S-transferases (GST) were found. Using isoelectric focusing we separated different forms of GST in tested tissues and revealed lower activities of the basic enzymes in Wilms' tumour, which may be responsible for the decrease of total GST activity. Moreover, we found the acidic isoenzymes to be the predominant class of GST in nephroblastoma. In Wilms' tumours with unfavourable histology a high activity of these isoenzymes together with a high level of GSH were observed. We suggest that these parameters may participate in the known phenomenon of anticancer drug resistance of tumours with unfavourable histology.
本研究展示了化疗(主要是放线菌素D和长春新碱)后肾母细胞瘤(肾胚胎瘤)样本中抗氧化酶和谷胱甘肽相关酶的活性以及谷胱甘肽水平。我们观察到,与相邻形态未改变的肾脏相比,肾母细胞瘤中超氧化物歧化酶的活性更高。另一方面,在该肿瘤中发现过氧化氢酶以及谷胱甘肽相关酶谷胱甘肽合成酶、γ-谷氨酰转肽酶、谷胱甘肽还原酶和总谷胱甘肽S-转移酶(GST)的活性较低。利用等电聚焦,我们在受试组织中分离出不同形式的GST,并发现肾母细胞瘤中碱性酶的活性较低,这可能是总GST活性降低的原因。此外,我们发现酸性同工酶是肾母细胞瘤中GST的主要类型。在组织学不良的肾母细胞瘤中,观察到这些同工酶的高活性以及高水平的谷胱甘肽。我们认为,这些参数可能参与了组织学不良肿瘤已知的抗癌药物耐药现象。