Song Yang, Leonard Scott W, Traber Maret G, Ho Emily
Department of Nutrition and Exercise Science and 5Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
J Nutr. 2009 Sep;139(9):1626-31. doi: 10.3945/jn.109.106369. Epub 2009 Jul 22.
Approximately 12% of Americans do not consume the Estimated Average Requirement for zinc and could be at risk for marginal zinc deficiency. Zinc is an essential component of numerous proteins involved in the defense against oxidative stress and DNA damage repair. Studies in vitro have shown that zinc depletion causes DNA damage. We hypothesized that zinc deficiency in vivo causes DNA damage through increases in oxidative stress and impairments in DNA repair. Sprague-Dawley rats were fed zinc-adequate (ZA; 30 mg Zn/kg) or severely zinc-deficient (ZD; <1 mg Zn/kg) diets or were pair-fed zinc-adequate diet to match the mean feed intake of ZD rats for 3 wk. After zinc depletion, rats were repleted with a ZA diet for 10 d. In addition, zinc-adequate (MZA 30 mg Zn/kg) or marginally zinc-deficient (MZD; 6 mg Zn/kg) diets were given to different groups of rats for 6 wk. Severe zinc depletion caused more DNA damage in peripheral blood cells than in the ZA group and this was normalized by zinc repletion. We also detected impairments in DNA repair, such as compromised p53 DNA binding and differential activation of the base excision repair proteins 8-oxoguanine glycosylase and poly ADP ribose polymerase. Importantly, MZD rats also had more DNA damage and higher plasma F(2)-isoprostane concentrations than MZA rats and had impairments in DNA repair functions. However, plasma antioxidant concentrations and erythrocyte superoxide dismutase activity were not affected by zinc depletion. These results suggest interactions among zinc deficiency, DNA integrity, oxidative stress, and DNA repair and suggested a role for zinc in maintaining DNA integrity.
约12%的美国人锌摄入量未达到估计平均需求量，可能存在边缘性锌缺乏风险。锌是众多参与抗氧化应激和DNA损伤修复的蛋白质的重要组成部分。体外研究表明，锌缺乏会导致DNA损伤。我们推测，体内锌缺乏通过增加氧化应激和损害DNA修复导致DNA损伤。将斯普拉格-道利大鼠分为三组，分别喂食锌充足（ZA；30毫克锌/千克）或严重锌缺乏（ZD；<1毫克锌/千克）的饲料，或与ZD大鼠平均采食量匹配的锌充足饲料，为期3周。锌缺乏后，大鼠再喂食ZA饲料10天。此外，将不同组的大鼠分别喂食锌充足（MZA 30毫克锌/千克）或边缘性锌缺乏（MZD；6毫克锌/千克）的饲料，为期6周。严重锌缺乏导致外周血细胞中的DNA损伤比ZA组更多，而补充锌后这种损伤得到了正常化。我们还检测到DNA修复存在缺陷，如p53与DNA的结合受损以及碱基切除修复蛋白8-氧鸟嘌呤糖基化酶和聚ADP核糖聚合酶的激活差异。重要的是，MZD大鼠的DNA损伤也比MZA大鼠更多，血浆F(2)-异前列腺素浓度更高，且DNA修复功能存在缺陷。然而，血浆抗氧化剂浓度和红细胞超氧化物歧化酶活性不受锌缺乏的影响。这些结果表明锌缺乏、DNA完整性、氧化应激和DNA修复之间存在相互作用，并提示锌在维持DNA完整性方面发挥作用。
