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 electrophoresis(SCGE),O~6-MeG was analyzed by high performance capillary zone electrophoresis.Results Spontaneous DNA damage had no differences in the four groups(P0.05).But DNA damage induced by 10μmol/L H_2O_2 had significant differences(P0.05).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 79.655AU(Arbitray units).The 5000mg/kgdiet VC supplement group was higher 28% than that of control group(P0.05)and the 10000mg/kgdiet VC supplement group was higher 49% than that of control group(P0601).The level of O~6-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(P0.05).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/kgdiet or ever higher,oxidative DNA damage induced by 10μmol/L H_2O_2 is significantly increased.Supplementing 10?000?mg/kgdiet VC can increase the level of O~6-MeG.