Effects of basal level of antioxidants on oxidative DNA damage in humans
Effects of basal level of antioxidants on oxidative DNA damage in humans
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DOI：
10.1007/s00394-006-0642-7
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发表时间：
2007-04-01
影响因子：
5
通讯作者：
Olinski, Ryszard
中科院分区：
文献类型：
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作者：
Foksinski, Marek;Gackowski, Daniel;Olinski, Ryszard
背景维生素A、E和C，以及可以清除自由基的尿酸，也应该保护DNA免受损伤。可以合理地认为，减少氧化DNA损伤的药物也应该减少随后的癌症发展。目的探讨抗氧化剂(维生素A、C、E和尿酸)的基础水平与DNA氧化损伤的关系。首次对158例健康受试者尿液中8-oxodG、8-oxoGua和5-HMUra的广谱DNA氧化损伤标志物以及白细胞DNA氧化损伤水平进行了分析。方法采用高效液相预纯化/同位素稀释GC/MS法检测尿液中DNA氧化损伤产物排泄量和白细胞DNA中8-oxodG的含量(采用高效液相色谱/电化学法)。抗氧化剂、维生素和尿酸的含量采用高效液相色谱荧光检测法和紫外检测法进行测定。结果分析最常见的抗氧化剂(维生素A、维生素C、维生素E和尿酸)与DNA氧化损伤产物的关系显示，除5HMUra外，视黄醇与所有测量参数呈微弱的、统计学上显著的负相关。维生素C与尿8-oxodG和8-oxogua排泄量呈负相关。尿酸与细胞DNA中8-oxodG和尿5HMUra排泄量呈显著负相关，而α-生育酚仅与细胞DNA中8-oxodG呈显著负相关。尿基8-氧鸟苷与脱氧核苷8-氧代葡萄糖苷呈良好的正相关关系(P<；0.0001)。结论我们的结果表明，DNA氧化损伤对抗氧化剂的反应有限但显著，而且更多地受到许多其他细胞功能的影响，如抗氧化酶或DNA修复酶以及遗传因素。
Background Vitamins A, E and C, and uric acid, which can scavenge free radicals should also protect DNA from the damage. It is reasonable to assume that agents that decrease oxidative DNA damage should also decrease subsequent cancer development. Aim of the study A relationship between basal level of antioxidants (vitamins A, C and E and uric acid) and oxidative DNA damage was assessed. For the first time, the broad spectrum of oxidative DNA damage biomarkers: urinary excretion of 8-oxodG, 8-oxoGua and 5HMUra as well as the level of oxidative DNA damage in leukocytes was analyzed in healthy subjects (n = 158). Methods Using HPLC prepurification/isotope dilution GC/MS methodology, we examined the amount of oxidative DNA damage products excreted into urine and the amount of 8-oxodG in leukocytes' DNA (with HPLC/EC technique). The level of antioxidant vitamins and uric acid was estimated by HPLC technique with fluorimetric and UV detection. Results Analyses of relationship between the most common antioxidants (vitamins A, C, E and uric acid) and oxidative DNA damage products reveal weak, statistically significant negative correlation between retinol and all the measured parameters except 5HMUra. Vitamin C negatively correlates with urinary excretion of 8-oxodG and 8-oxoGua. Uric acid revealed statistically significant negative correlation with 8-oxodG in cellular DNA and urinary excretion of 5HMUra, while alpha-tocopherol correlates negatively only with 8-oxodG in cellular DNA. Good, significant (P < 0.0001), positive correlation (r = 0.61) was noted between urinary levels of the base, 8-oxoGua and the deoxynucleoside, 8-oxodG. Conclusion Our results suggest that oxidative DNA damage shows limited but significant response to antioxidants analyzed in this study and is more affected by many other cellular functions like antioxidant enzymes or DNA repair enzymes as well as genetics.