Department of Oncology, Complejo Hospitalario de Jaen, Jaen, Spain.
Free Radic Res. 2012 Jan;46(1):2-10. doi: 10.3109/10715762.2011.635658. Epub 2011 Nov 18.
Antineoplastic agents are known to induce the production of free radicals leading to cell damage. These adverse effects may fuel the acquisition of new mutations and the development of treatment resistances. We selected 30 metastatic breast cancer patients receiving palliative chemotherapy, and paired blood samples, before and after chemotherapy, were extracted. We analysed DNA, lipid and protein oxidative damage markers and determined the extent of antioxidant and repair defences activation at the systemic level. We found that the DNA repair activity of the KU86 enzyme was significantly lower after chemotherapy and the antioxidant capacity of the plasma was significantly higher after treatment. Cox regression analysis revealed a significant effect of KU86 activity on the survival rates of those patients who received anthracyclines as part of their treatment. The high clinical heterogeneity of metastatic breast cancer patients warrants further studies to clarify the role of DNA repair and systemic antioxidant capacities during chemotherapy.
抗肿瘤药物已知会诱导自由基的产生,导致细胞损伤。这些不良反应可能会促进新突变的获得和治疗耐药性的发展。我们选择了 30 名接受姑息化疗的转移性乳腺癌患者,并提取了化疗前后的配对血液样本。我们分析了 DNA、脂质和蛋白质氧化损伤标志物,并确定了系统水平上抗氧化和修复防御的激活程度。我们发现,化疗后 KU86 酶的 DNA 修复活性显著降低,治疗后血浆的抗氧化能力显著升高。Cox 回归分析显示,KU86 活性对接受蒽环类药物作为治疗一部分的患者的生存率有显著影响。转移性乳腺癌患者的临床异质性很高,需要进一步的研究来阐明化疗过程中 DNA 修复和系统抗氧化能力的作用。