Smolková B, Dusinská M, Raslová K, Barancoková M, Kazimírová A, Horská A, Spustová V, Collins A
Research Base of Slovak Medical University, Institute of Preventive and Clinical Medicine, Limbová 12, Bratislava 83303, Slovakia.
Mutagenesis. 2004 Nov;19(6):469-76. doi: 10.1093/mutage/geh059.
We have investigated the effect of modest supplementation with alpha-tocopherol (100 mg/day), beta-carotene (6 mg/day), vitamin C (100 mg/day) and selenium (50 microg/day) on oxidative stress and chromosomal damage, and the influence of methylenetetrahydrofolate reductase (MTHFR) genotype on these end-points. Subjects were two groups of middle-aged men differing in cardiovascular risk; 46 survivors of myocardial infarction before age 50 and 60 healthy controls. They were randomly divided into equal groups to receive antioxidants or placebo for 12 weeks. Twenty-eight patients and 58 controls completed the intervention. Micronucleus levels in peripheral lymphocytes and changes seen after intervention were studied in relation to the MTHFR C677T genotype, basal homocysteine and plasma folate levels. Ferric reducing ability of plasma and concentration of malondialdehyde were measured to assess the antioxidant effect of supplementation. There was no association of micronuclei with folate, homocysteine or malondialdehyde levels before supplementation. Micronucleus frequencies and plasma folate levels did not vary significantly with MTHFR genotype. Homocysteine levels in subjects with the TT variant genotype were significantly higher compared with CT or CC (P = 0.001), especially in subjects with low folate (P = 0.012). In the placebo control group an increase in micronuclei (P = 0.04) was detected at the end of the intervention period. This effect was not seen in the supplemented group. In antioxidant-supplemented myocardial infarction survivors we found an increase in the ferric reducing ability of plasma (P < 0.001) and a decrease in malondialdehyde (P = 0.001). Micronucleus frequency showed a decrease, strongest in subjects with normal folate levels (P = 0.015). In subjects with low folate levels, a high correlation was found between micronuclei after supplementation and homocysteine, both before (r = 0.979, P = 0.002) and after supplementation (r = 0.922, P = 0.009). Thus, folate deficiency may amplify the effect of other risk factors such as elevated homocysteine levels or variant MTHFR genotype, as well as influencing the ability of antioxidant supplementation to protect against genetic damage.
我们研究了适度补充α-生育酚（100毫克/天）、β-胡萝卜素（6毫克/天）、维生素C（100毫克/天）和硒（50微克/天）对氧化应激和染色体损伤的影响，以及亚甲基四氢叶酸还原酶（MTHFR）基因型对这些终点指标的影响。受试者为两组心血管风险不同的中年男性；46名50岁前心肌梗死幸存者和60名健康对照者。他们被随机分为相等的组，接受抗氧化剂或安慰剂治疗12周。28名患者和58名对照者完成了干预。研究了外周淋巴细胞中的微核水平以及干预后观察到的变化与MTHFR C677T基因型、基础同型半胱氨酸和血浆叶酸水平的关系。测量血浆的铁还原能力和丙二醛浓度以评估补充剂的抗氧化作用。补充前微核与叶酸、同型半胱氨酸或丙二醛水平无关联。微核频率和血浆叶酸水平随MTHFR基因型无显著变化。TT变异基因型受试者的同型半胱氨酸水平显著高于CT或CC基因型受试者（P = 0.001），尤其是叶酸水平低的受试者（P = 0.012）。在安慰剂对照组中，干预期末检测到微核增加（P = 0.04）。补充剂组未观察到这种效应。在补充抗氧化剂的心肌梗死幸存者中，我们发现血浆铁还原能力增加（P < 0.001），丙二醛减少（P = 0.001）。微核频率下降，在叶酸水平正常的受试者中下降最为明显（P = 0.015）。在叶酸水平低的受试者中，补充后微核与同型半胱氨酸之间在补充前（r = 0.979，P = 0.002）和补充后（r = 0.922，P = 0.009）均发现高度相关。因此，叶酸缺乏可能会放大其他风险因素的影响，如升高的同型半胱氨酸水平或变异的MTHFR基因型，以及影响抗氧化剂补充剂预防遗传损伤的能力。
