Hu J J, Chi C X, Frenkel K, Smith B N, Henfelt J J, Berwick M, Mahabir S, D'Agostino R B
Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA.
Cancer Epidemiol Biomarkers Prev. 1999 Aug;8(8):693-8.
This study evaluated the effects of vitamin E (alpha-tocopherol) on oxidative DNA damage in a randomized double-blind Phase II chemoprevention trial. Oxidative DNA damage was measured by the level of auto-antibody (Ab) against 5-hydroxymethyl-2'-deoxyuridine (HMdU) in plasma. After the baseline screening, eligible subjects (n = 31; plasma samples from 28 subjects were available for this study) were randomized to receive 15, 60, or 200 mg of alpha-tocopherol per day for 28 days. Biomarkers were measured twice at baseline--on day 1 (visit 1) and day 3 (visit 2)--and twice after intervention--on day 17 (visit 3) and day 31 (visit 4). At baseline, there was a highly significant inverse correlation between anti-HMdU Ab titer and plasma vitamin E level (r = -0.53; P = 0.004; n = 28). Smoking did not affect baseline anti-HMdU Ab titer; however, anti-HMdU Ab titer levels at baseline were significantly lower in subjects with above-median (0.75 ounce/day) alcohol consumption (P = 0.008). No significant change in anti-HMdU Ab level occurred at either visit 3 or visit 4 for subjects on the lowest dose, 15 mg alpha-tocopherol per day. Subjects receiving 60 mg of alpha-tocopherol per day had a significant decrease in anti-HMdU Ab level at visits 3 and 4 compared with baseline (P = 0.049 and P = 0.02, respectively). However, subjects receiving the highest dose, 200 mg/day, had less consistent results: a significant decrease in anti-HMdU Ab level was seen at visit 4 (P = 0.04) but not at visit 3. Our results demonstrate an inverse relationship between alpha-tocopherol and anti-HMdU Abs in plasma; oxidative DNA damage can be modulated by short-term dietary supplementation of alpha-tocopherol in some subjects.
在一项随机双盲II期化学预防试验中，本研究评估了维生素E（α-生育酚）对氧化性DNA损伤的影响。通过血浆中抗5-羟甲基-2'-脱氧尿苷（HMdU）自身抗体（Ab）水平来测定氧化性DNA损伤。在基线筛查后，符合条件的受试者（n = 31；本研究可获得28名受试者的血浆样本）被随机分为三组，分别每天接受15毫克、60毫克或200毫克的α-生育酚，持续28天。在基线时（第1天[访视1]和第3天[访视2]）以及干预后（第17天[访视3]和第31天[访视4]）对生物标志物进行了两次测量。在基线时，抗HMdU Ab滴度与血浆维生素E水平之间存在高度显著的负相关（r = -0.53；P = 0.004；n = 28）。吸烟不影响基线抗HMdU Ab滴度；然而，酒精摄入量高于中位数（0.75盎司/天）的受试者基线抗HMdU Ab滴度水平显著较低（P = 0.008）。对于每天服用最低剂量15毫克α-生育酚的受试者，在访视3或访视4时抗HMdU Ab水平均未发生显著变化。每天接受60毫克α-生育酚的受试者在访视3和访视4时，与基线相比抗HMdU Ab水平显著降低（分别为P = 0.049和P = 0.02）。然而，接受最高剂量（200毫克/天）的受试者结果不太一致：在访视4时抗HMdU Ab水平显著降低（P = 0.04），但在访视3时未降低。我们的结果表明血浆中α-生育酚与抗HMdU Abs之间存在负相关；在一些受试者中，短期饮食补充α-生育酚可调节氧化性DNA损伤。
