大剂量维生素C对DNA氧化烷化损伤影响
Effect of high-dose Vitamin C supplement on DNA oxidative and alkylating damage in rats
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摘要:目的 观察大剂量摄入维生素C(VC)对DNA氧化损伤及烷化损伤的影响。方法 以补充大剂量VC饲料给幼年Wistar大鼠, 剂量分别为0, 2 000, 5 000, 10 000mg/kg饲料, 不添加VC作为对照组, 干预时间为60 d。干预结束后, 采用单细胞凝胶电泳法检测和评价淋巴细胞DNA自发损伤和H2O2诱导的氧化损伤; 留取尿液用毛细管电泳法检测大鼠尿中O6-甲基鸟嘌呤(O6-methyl guanine, O6-MeG)含量。结果 各组大鼠的DNA自发损伤差异无统计学意义(P > 0.05)。10μmol/L的H2O2诱发DNA损伤时, 随剂量增加, DNA损伤逐渐加重, 对照组为59.060AU, 2 000 mg/kg饲料剂量组为69.900AU, 5000 mg/kg饲料剂量组为75.768AU, 比对照组升高28%(P < 0.05), 10000 mg/kg饲料剂量组为79.655AU, 比对照组升高49%(P < 0.01)。各组O6-MeG的含量差异有统计学意义(P=0.01), 10 000m g/kg饲料剂量组含量最高为2.434 mg/g肌酐, 比对照组升高36%(P < 0.05)。结论 高剂量VC对DNA自发损伤没有影响, 而对10μmol/L H2O2的诱导损伤, 补充5 000 mg/kg饲料和10 000 mg/kg饲料的VC可加重DNA损伤。给大鼠补充10 000 mg/kg饲料的VC可导致DNA烷化损伤产物O6-MeG生成增多。Abstract:Objective To investigate the effects of high-dose vitamin C(VC)on DNA oxidative and alkylating damage.Methods Healthy young rats were randomized into 4 groups.They were supplemented with different dose of VC(0, 2000, 5000, 10000 mg/kg diet).The first group was control.The period of the trail was 60 days.Urine was collected in the mid of the trial and whole blood was collected by the end of the trial.DNA damage were analyzed by single cell gel electrophor esis(SCGE), O6-MeG was analyzed by high per for mance capillary zone electrophoresis.Results Spontaneous DNA damage had no differences in the four groups(P > 0.05).But DNA damage induced by 10μmol/L H2O2 had significant differences(P < 0.05).The DNA damage was gradually increased with the VC dose's adding.The DNA damage of the four groups was separately 59.060, 69.900, 75.768 and 79.655 AU(Arbitray units).The 5000mg/kg diet VC supplement group was higher 28% than that of control group(P < 0.05)and the 10000mg/kgdiet VC supplement group was higher 49% than that of control group(P < 0.601).The level of O6-MeG in the 10 000 mg/kgdiet VC supplement group was the highest (2.434mg/g.creatinine)and higher 36% than that of control group(P < 0.05).Conclusion Different high-doses of vitamin C have no effect on the spontaneous DNA damage.When the supplementing dose of VC is rose to 5 000 mg/kg diet or ever higher, oxidative DNA damage induced by 10μmol/L H2O2 is significantly increased.Supplementing 10 000 mg/kg diet VC can increase the level of O6-MeG.
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