Poulsen H E, Loft S, Prieme H, Vistisen K, Lykkesfeldt J, Nyyssonen K, Salonen J T
Department of Clinical Pharmacology, Rigshospitalet, University Hospital Copenhagen, Denmark.
Free Radic Res. 1998 Dec;29(6):565-71. doi: 10.1080/10715769800300601.
Oxidative DNA modification has been implicated in development of certain cancers and 8-oxodG, the most abundant and mutagenic DNA modification, has for some time been considered a biomarker of this activity. Urinary excretion of 8-oxodG over 24h has been used to estimate the rate of damage to DNA, and animal studies have supported this rationale. Reported determinants include tobacco smoking, heavy exercise, environmental pollution and individual oxygen consumption. Samples from three published studies were used to determine the association of urinary 8-oxodG excretion with age, plasma antioxidants, the glutathione-S-transferase phenotype and the activity of the xenobiotic metabolising enzyme CYP1A2. In the age range 35-65 years, age was not related to urinary 8-oxodG excretion, and there were no relations to either the glutathione-S-transferase phenotype or to the plasma antioxidants: vitamin C, alpha-tocopherol, beta-carotene, lycopene or coenzyme Q10. The activity of CYP1A2 showed a significant correlation in two of the three studies, as well as a significant correlation of 0.26 (p < 0.05) in the pooled data set. Regression analysis of CYP1A2 activity on 8-oxodG indicated that 33% increase in CYP1A2 activity would correspond to a doubling of 8-oxodG excretion. This finding needs to be confirmed in independent experiments. Spot morning urine samples can under certain circumstances be used to estimate 8-oxodG excretion rate provided that creatinine excretion is unchanged (in paired experiments) or comparable (in un-paired experiments), as evaluated from the correlation between 8-oxodG excretion in 24 h urine samples and in morning spot urine samples corrected for creatinine excretion (r = 0.50, p < 0.05). We conclude that 8-oxodG excretion is determined by factors like oxygen consumption and CYP1A2 activity rather than by factors like plasma antioxidant concentrations.
氧化DNA修饰与某些癌症的发生有关，而8-氧代脱氧鸟苷（8-oxodG）是最丰富且具有致突变性的DNA修饰，一段时间以来一直被视为这种活性的生物标志物。24小时内8-oxodG的尿排泄量已被用于估计DNA的损伤速率，动物研究也支持了这一理论依据。报告的决定因素包括吸烟、剧烈运动、环境污染和个体耗氧量。来自三项已发表研究的样本被用于确定尿8-oxodG排泄量与年龄、血浆抗氧化剂、谷胱甘肽-S-转移酶表型以及外源性代谢酶CYP1A2活性之间的关联。在35至65岁的年龄范围内，年龄与尿8-oxodG排泄量无关，与谷胱甘肽-S-转移酶表型或血浆抗氧化剂（维生素C、α-生育酚、β-胡萝卜素、番茄红素或辅酶Q10）也均无关联。CYP1A2的活性在三项研究中的两项显示出显著相关性，在汇总数据集中也有显著的0.26的相关性（p < 0.05）。对CYP1A2活性与8-oxodG进行回归分析表明，CYP1A2活性增加33%将对应8-oxodG排泄量翻倍。这一发现需要在独立实验中得到证实。在某些情况下，只要肌酐排泄量不变（在配对实验中）或可比（在非配对实验中），晨尿样本就可用于估计8-oxodG排泄率，这是根据24小时尿样和经肌酐排泄校正的晨尿样本中8-oxodG排泄量之间的相关性评估得出的（r = 0.50，p < 0.05）。我们得出结论，8-oxodG排泄量是由耗氧量和CYP1A2活性等因素决定的，而非血浆抗氧化剂浓度等因素。
