Cadenas S, Barja G, Poulsen H E, Loft S
Department of Pharmacology, Panum Institute, University of Copenhagen, Copenhagen N, Denmark.
Carcinogenesis. 1997 Dec;18(12):2373-7. doi: 10.1093/carcin/18.12.2373.
Dietary antioxidants may influence cancer risk and aging by modifying oxidative damage. The effect of graded dietary doses of the antioxidant vitamins C and E on oxidative DNA damage was studied in the liver of guinea-pigs under normal conditions. Like human beings, guinea-pigs cannot synthesize ascorbate and alpha-tocopherol. In one experiment, three 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 guinea-pigs were fed diets containing 660 mg of vitamin C/kg and three different amounts of vitamin E (15, 150 or 1500 mg/kg) for 5 weeks. The three graded levels of each vitamin respectively represent marginal deficiency, an optimum supplementation and a megadose. Oxidative damage to liver DNA was estimated by measuring 8-oxo-7,8-dihydro-2'-deoxyguanosine (oxo8dG) referred to deoxyguanosine (dG) by means of high-performance liquid chromatography with simultaneous electrochemical-coulometric and ultraviolet detection. The level of ascorbate in the liver was 0.034 +/- 0.051, 1.63 +/- 1.06 and 1.99 +/- 0.44 micromol/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 alpha-tocopherol groups (7-fold variation). The level of oxo8dG 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 high dose ascorbate groups (no effect: P > 0.05). In the low, medium and high dose alpha-tocopherol groups oxo8dG 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 content of the antioxidant vitamins C and E in the diet and liver have no influence on the steady-state level of oxidative damage to guanine in the liver DNA of normal unstressed guinea-pigs.
膳食抗氧化剂可能通过改变氧化损伤来影响癌症风险和衰老。在正常条件下，研究了不同剂量的抗氧化维生素C和E对豚鼠肝脏氧化DNA损伤的影响。与人类一样，豚鼠不能合成抗坏血酸和α-生育酚。在一项实验中，将三组6 - 8只豚鼠喂养含15毫克维生素E/千克饲料和三种不同剂量维生素C（33、660或13200毫克/千克）的饲料，持续5周。在第二项实验中，将三组7只豚鼠喂养含660毫克维生素C/千克和三种不同剂量维生素E（15、150或1500毫克/千克）的饲料，持续5周。每种维生素的三个分级水平分别代表边缘性缺乏、最佳补充剂量和超大剂量。通过高效液相色谱同时进行电化学 - 库仑法和紫外检测，测量8 - 氧代 - 7,8 - 二氢 - 2'-脱氧鸟苷（oxo8dG）与脱氧鸟苷（dG）的比值来估计肝脏DNA的氧化损伤。低、中、高剂量抗坏血酸组肝脏中抗坏血酸水平分别为0.034±0.051、1.63±1.06和1.99±0.44微摩尔/克（变化59倍）。低、中、高剂量α - 生育酚组肝脏中α - 生育酚浓度分别为28±11、63±18和187±34纳摩尔/克（变化7倍）。低、中、高剂量抗坏血酸组肝脏DNA中oxo8dG水平分别为每1×10⁵ dG 1.89±0.32、1.94±0.78和1.93±0.65（无影响：P＞0.05）。低、中、高剂量α - 生育酚组肝脏DNA中oxo8dG水平分别为每1×10⁵ dG 2.85±0.70、2.74±0.66和2.61±0.92（无影响：P＞0.05）。结论是，即使饮食和肝脏中抗氧化维生素C和E的含量有很大差异，对正常无应激豚鼠肝脏DNA中鸟嘌呤的氧化损伤稳态水平也没有影响。
