Duthie S J, Ma A, Ross M A, Collins A R
Rowett Research Institute, Bucksburn, Aberdeen, Scotland, United Kingdom.
Cancer Res. 1996 Mar 15;56(6):1291-5.
The association between high intake of fruit and vegetables and low incidence of certain cancers is well established. Dietary antioxidants present in these foods are thought to decrease free radical attack on DNA and hence to protect against mutations that cause cancer, but this causal mechanism remains conjectural. We have adopted a molecular epidemiological approach to this question, based on a modified alkaline single-cell gel electrophoresis assay ("comet assay") which specifically detects oxidation of pyrimidines in the DNA of human lymphocytes. In a survey of men 50-59 years of age living in the northeast of Scotland, smokers initially showed significantly more base damage than nonsmokers. Correlations between oxidative base damage and plasma concentrations of various antioxidants were generally negative but not statistically significant. Supplementation of the diet for 20 weeks with vitamin C (100 mg/day), vitamin E (280 mg/day), and beta-carotene (25 mg/day) resulted in a highly significant (P < 0.002) decrease in endogenous oxidative base damage in the lymphocyte DNA of both smokers and nonsmokers. In addition, lymphocytes of antioxidant-supplemented subjects showed an increased resistance to oxidative damage when challenged in vitro with H2O2. These findings strongly support the hypothesis that fruit and vegetables exert a cancer-protective effect via a decrease in oxidative damage to DNA.
大量摄入水果和蔬菜与某些癌症的低发病率之间的关联已得到充分证实。这些食物中含有的膳食抗氧化剂被认为可减少自由基对DNA的攻击，从而预防导致癌症的突变，但这种因果机制仍属推测。我们采用了一种分子流行病学方法来研究这个问题，该方法基于一种改良的碱性单细胞凝胶电泳分析（“彗星试验”），它能特异性检测人类淋巴细胞DNA中嘧啶的氧化。在对居住在苏格兰东北部50至59岁男性的一项调查中，吸烟者最初显示出比不吸烟者明显更多的碱基损伤。氧化碱基损伤与各种抗氧化剂血浆浓度之间的相关性通常为负，但无统计学意义。用维生素C（100毫克/天）、维生素E（280毫克/天）和β-胡萝卜素（25毫克/天）对饮食进行20周的补充，导致吸烟者和不吸烟者淋巴细胞DNA中的内源性氧化碱基损伤均显著降低（P < 0.002）。此外，补充抗氧化剂的受试者的淋巴细胞在体外受到过氧化氢攻击时，对氧化损伤的抵抗力增强。这些发现有力地支持了水果和蔬菜通过减少对DNA的氧化损伤发挥防癌作用这一假说。
