Collins A R, Gedik C M, Olmedilla B, Southon S, Bellizzi M
Rowett Research Institute, Bucksburn, Aberdeen AB21 9SB, United Kingdom.
FASEB J. 1998 Oct;12(13):1397-400.
The 'antioxidant hypothesis' proposes that vitamin C, vitamin E, carotenoids, and other antioxidants occurring in fruit and vegetables afford protection against heart disease and cancer by preventing oxidative damage to lipids and to DNA, respectively. To test elements of this hypothesis, we have measured blood levels of dietary antioxidants, and 8-oxodeoxyguanosine (8-oxo-dG) concentrations in lymphocyte DNA, in healthy men and women from five European countries: France, Ireland, The Netherlands, Spain, and the U.K. Volunteers, aged 25 45, all nonsmokers, gave blood samples before and after a 12-wk carotenoid supplementation regime. Vitamin C was measured in plasma and vitamin E and carotenoids were measured in serum by high-performance liquid chromatography (HPLC). 8-oxo-dG was assayed by HPLC (with coulometric detection) in DNA isolated from lymphocytes from the same blood samples. Mean values were calculated for groups of volunteers at each sampling time according to country, sex, and supplementation (between 9 and 24 individual samples contributing to each mean). We found that 8-oxo-dG levels in lymphocyte DNA vary significantly according to sex and country. A low mean 8-oxo-dG concentration is seen in DNA of women from all five countries, and of men from France and Spain. 8-oxo-dG is significantly higher (up to about threefold) in lymphocyte DNA from men in Ireland and the U.K. Oxidative DNA damage is not significantly affected by carotenoid supplementation; nor is there any association with mean baseline levels of antioxidants, which are generally similar in the five countries. The five countries sampled lie on an axis from northern to southern Europe with a steep gradient in terms of premature heart disease. There is a strong association between premature coronary heart disease mortality in men and the mean levels of 8-oxo-dG for the five countries (r = 0.95, P < 0.01). Women have low coronary heart disease mortality rates, which do not correlate with 8-oxo-dG. In terms of cancer deaths, only colorectal cancer in men shows a significant positive correlation (r = 0.91, P < 0.05), and stomach cancer in women is negatively correlated with DNA oxidation (r = -0.92, P = 0.01).
“抗氧化假说”提出，水果和蔬菜中含有的维生素C、维生素E、类胡萝卜素及其他抗氧化剂，分别通过防止脂质和DNA的氧化损伤，来预防心脏病和癌症。为验证该假说的要点，我们测量了来自法国、爱尔兰、荷兰、西班牙和英国这五个欧洲国家的健康男性和女性的膳食抗氧化剂血液水平，以及淋巴细胞DNA中的8-氧代脱氧鸟苷（8-oxo-dG）浓度。年龄在25至45岁之间、均为非吸烟者的志愿者，在进行为期12周的类胡萝卜素补充方案前后提供血样。通过高效液相色谱法（HPLC）测量血浆中的维生素C以及血清中的维生素E和类胡萝卜素。通过HPLC（采用库仑检测法）对从相同血样的淋巴细胞中分离出的DNA中的8-oxo-dG进行检测。根据国家、性别和补充情况（每组平均值由9至24个个体样本得出），计算每个采样时间志愿者组的平均值。我们发现，淋巴细胞DNA中的8-oxo-dG水平因性别和国家的不同而有显著差异。在所有五个国家的女性以及法国和西班牙男性的DNA中，均可见到较低的8-oxo-dG平均浓度。在爱尔兰和英国男性的淋巴细胞DNA中，8-oxo-dG显著更高（高达约三倍）。类胡萝卜素补充对氧化性DNA损伤没有显著影响；也与抗氧化剂的平均基线水平没有关联，这五个国家的抗氧化剂平均基线水平总体相似。所采样的这五个国家位于从北欧到南欧的一条轴线上，在早发性心脏病方面存在陡峭的梯度。男性早发性冠心病死亡率与这五个国家的8-oxo-dG平均水平之间存在很强的关联（r = 0.95，P < 0.01）。女性冠心病死亡率较低，与8-oxo-dG没有相关性。在癌症死亡方面，仅男性的结直肠癌显示出显著的正相关（r = 0.91，P < 0.05），女性的胃癌与DNA氧化呈负相关（r = -0.92，P = 0.01）。
