Laboratory of Industrial Toxicology, Department of Clinical Medicine, Nephrology, and Health Sciences, ISPESL-National Institute for Occupational Safety and Prevention, Research Center, University of Parma, Parma, Italy.
Free Radic Biol Med. 2011 Jan 15;50(2):254-61. doi: 10.1016/j.freeradbiomed.2010.11.009. Epub 2010 Nov 11.
This study was aimed at defining the reference ranges for biomarkers of oxidized guanine in (2'-deoxy)ribonucleotides and nucleic acids from a large Italian sample. We recruited 300 healthy subjects (150 males; mean age 44.1±13.6years; 26% smokers) without any known exposure to occupational oxidizing agents. They were asked to provide a spot urine sample, on which the following markers were determined by liquid chromatography-tandem mass spectrometry: 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), 8-oxo-7,8-dihydroguanosine (8-oxoGuo), 8-oxo-7,8-dihydroguanine (8-oxoGua), and cotinine. The reference ranges, estimated as the 5th-95th percentiles of creatinine-normalized values (pmol/μmol(creat)) were 0.7-4.2, 0.9-4.7, and 5.6-120.7 for 8-oxodGuo, 8-oxoGuo, and 8-oxoGua, respectively. Oxidation biomarkers were correlated with one another (p<0.005) and with urinary creatinine (p<0.0001). Males excreted significantly higher concentrations of 8-oxoGua than females (p<0.0001). 8-OxoGua and 8-oxoGuo showed a positive association with age (p<0.001), also after stratification by gender. Multiple linear regression models including urinary creatinine concentration, age, and smoking habit as independent variables showed a significant effect of age, but not of smoking, on the levels of 8-oxoGuo in males (p<0.0001) and of both 8-oxoGuo and 8-oxoGua in females (p<0.0001). A preliminary assessment in a small group (n=25) of patients affected by advanced non-small-cell lung cancer and receiving platinum-based chemotherapy showed significantly higher values of both 8-oxoGuo and 8-oxodGuo (p<0.0001 for both) compared to the referent population.
本研究旨在为意大利大样本的（2'-脱氧）核糖核苷酸和核酸中氧化鸟嘌呤生物标志物定义参考范围。我们招募了 300 名健康受试者（150 名男性；平均年龄 44.1±13.6 岁；26%为吸烟者），他们没有任何已知的职业氧化剂暴露。要求他们提供一份尿样，通过液相色谱-串联质谱法测定以下标志物：8-氧代-7,8-二氢-2'-脱氧鸟苷（8-氧代 dGuo）、8-氧代-7,8-二氢鸟苷（8-氧代 Guo）、8-氧代-7,8-二氢鸟嘌呤（8-氧代 Gua）和可替宁。以肌酐标准化值（pmol/μmol（creat））的第 5-95 百分位数估计的参考范围分别为 8-氧代 dGuo、8-氧代 Guo 和 8-氧代 Gua 的 0.7-4.2、0.9-4.7 和 5.6-120.7。氧化生物标志物彼此相关（p<0.005），且与尿肌酐相关（p<0.0001）。男性排泄的 8-氧代 Gua 浓度明显高于女性（p<0.0001）。8-氧代 Gua 和 8-氧代 Guo 与年龄呈正相关（p<0.001），且按性别分层后也呈正相关。以尿肌酐浓度、年龄和吸烟习惯为自变量的多元线性回归模型显示，年龄对男性 8-氧代 Guo（p<0.0001）和女性 8-氧代 Guo 和 8-氧代 Gua（p<0.0001）水平有显著影响，但吸烟无影响。在一小部分（n=25）接受铂类化疗的晚期非小细胞肺癌患者中的初步评估显示，与参照人群相比，8-氧代 Guo 和 8-氧代 dGuo 的水平均显著升高（两者均为 p<0.0001）。
