OXIDATIVE DNA-DAMAGE ESTIMATED BY OXO(8)DG IN THE LIVER OF GUINEA-PIGS SUPPLEMENTED WITH GRADED DIETARY DOSES OF ASCORBIC-ACID AND ALPHA-TOCOPHEROL

Dietary antioxidants may influence cancer risk and aging by modifying oxidative damage, The effect of graded dietary doses of the antioxidan t vitamins C and E on oxidative DNA damage was studied in the liver of guineapigs under normal conditions, Like human beings, guineapigs can not synthesize ascorbate and alpha-tocopherol, In one experiment, thre e groups of 6-8 guinea-pigs were fed diets containing 15 mg of vitamin E/kg chow and three different amounts of vitamin C (33 660 or 13 200 mg/kg) for 5 weeks, In a second experiment, three groups of seven guin ea-pigs were fed diets containing 660 mg of vitamin C/kg and three dif ferent amounts of vitamin E (15, 150 or 1500 mg/kg) for 5 weeks, The t hree graded levels of each vitamin respectively represent marginal def iciency, an optimum supplementation and a megadose, Oxidative damage t o liver DNA was estimated by measuring 8-oxo-7,8-dihydro-2'-deoxyguano sine (oxo(8)dG) referred to deoxyguanosine (dG) by means of high-perfo rmance liquid chromatography with simultaneous electrochemical-coulome tric and ultraviolet detection, The level of ascorbate in the liver wa s 0.034 +/- 0.051, 1.63 +/- 1.06 and 1.99 +/- 0.44 mu mol/g in the low medium and high dose ascorbate groups (59-fold variation), The liver concentration of alpha-tocopherol was 28 +/- 11, 63 +/- 18 and 187 +/- 34 nmol/g in the low medium and high dose a-tocopherol groups (7-fold variation), The level of oxo(8)dG in the Liver DNA was 1.89 +/- 0.32, 1.94 +/- 0.78 and 1.93 +/- 0.65 per 10(5) dG in the low medium and hi gh dose ascorbate groups (no effect: P > 0.05), In the low medium and high dose alpha-tocopherol groups oxo(8)dG level in the liver DNA was 2.85 +/- 0.70, 2.74 +/- 0.66 and 2.61 +/- 0.92 per 10(5) dG (no effect : P > 0.05), It is concluded that even very large variations in the co ntent of the antioxidant vitamins C and E in the diet and liver have n o influence on the steady-state level of oxidative damage to guanine i n the liver DNA of normal unstressed guinea-pigs.