Department of Clinical Biochemistry, Collegium Medicum, Nicolaus Copernicus University, Karłowicza 24, Bydgoszcz, Poland.
Cancer Epidemiol Biomarkers Prev. 2012 Apr;21(4):629-34. doi: 10.1158/1055-9965.EPI-11-0981. Epub 2012 Feb 1.
Because of the importance to identify prognostic indicator for radiotherapy, herein we decided to check whether the parameters which describe oxidative stress/DNA damage may be used as a marker of the therapy. The aim of this work was to investigate whether fractionated radiotherapy of patients with cancer (n = 99) is responsible for oxidative DNA damage on the level of the whole organism and whether the biomarkers of the damage such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and its modified base 8-oxo-7,8-dihydroguanine (8-oxo-Gua) in urine and DNA may be used as a predictor of radiotherapy success.
All the aforementioned modifications were analyzed using techniques which involve high-performance liquid chromatography/electrochemical detection (HPLC/EC) or HPLC/gas chromatography-mass spectroscopy (GC-MS).
Of all analyzed parameters only patients with significantly elevated urinary excretion of the 8-oxo-Gua with concomitant unchanged level of 8-oxo-dG in leukocytes DNA in the samples collected 24 hours after the first fraction in comparison to the initial level have significantly increased survival time (60 months after the treatment, survival of 50% of the patients who fulfill the above mentioned criteria, in comparison with 10% of the patients who did not).
Results of our work suggest that patients with higher urinary 8-oxo-Gua and concomitant stable level of 8-oxo-dG in leukocytes DNA, after 24 hours of the first dose should be regarded as better responder to radiotherapy as being at lower risk of mortality.
The above mentioned statement could make it possible to use these parameters as markers to predict the clinical success.
由于识别放疗预后指标非常重要,因此我们决定检查描述氧化应激/DNA 损伤的参数是否可用作治疗标志物。本工作旨在研究癌症患者(n=99)的分次放疗是否会导致整个机体的氧化 DNA 损伤,以及尿液和 DNA 中损伤的生物标志物如 8-氧代-7,8-二氢-2'-脱氧鸟苷(8-oxo-dG)和其修饰碱基 8-氧代-7,8-二氢鸟嘌呤(8-oxo-Gua)是否可用作放疗成功的预测因子。
使用涉及高效液相色谱/电化学检测(HPLC/EC)或高效液相色谱/气相色谱-质谱联用(HPLC/GC-MS)的技术分析所有上述修饰。
在所分析的参数中,只有在第一次分割后 24 小时收集的样本中白细胞 DNA 中 8-oxo-Gua 的尿排泄量显著升高,而 8-oxo-dG 水平不变的患者,与初始水平相比,生存时间显著延长(治疗后 60 个月,符合上述标准的患者中有 50%存活,而不符合的患者只有 10%)。
我们的工作结果表明,在第一次剂量后 24 小时,尿液中 8-oxo-Gua 较高且白细胞 DNA 中 8-oxo-dG 水平稳定的患者,对放疗的反应较好,死亡风险较低。
上述说法可以使这些参数作为预测临床成功的标志物。