Department of Public Health and Environmental Medicine, Faculty of Medicine, The Jikei University School of Medicine, 3-25-8 Nishishimbashi, Minato-ku, Tokyo 105-8461, Japan.
Biol Trace Elem Res. 2013 Jul;154(1):120-6. doi: 10.1007/s12011-013-9706-8. Epub 2013 May 29.
The aim of the present study was to examine whether zinc (Zn) deficiency augmented the frequency of micronuclei, an indicator of chromosome aberration, and the induction of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of cellular DNA damage derived from oxidative stress, in rat bone marrow cells or not. Both the frequency of micronuclei and the induction of 8-OHdG were significantly increased in rats fed with a Zn-deficient versus a standard diet for 6 weeks (p < 0.005). The supplementation of Zn with a standard diet for 4 weeks to rats fed with a Zn-deficient diet for 6 weeks restored the enhanced induction of micronuclei and 8-OHdG to levels comparable to those seen in rats fed with a standard diet for 10 weeks, indicating that the shortage of Zn in the body is involved in the induction of micronuclei and 8-OHdG. Again, the membrane-permeable superoxide dismutase mimetic superoxide scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl, treatment (100 μmol/kg, twice a day) for 10 days prior to the termination of dietary treatment reduced the induction of micronuclei and 8-OHdG in rats fed with a Zn-deficient diet for 6 weeks to levels comparable to those in rats fed with a standard diet for 6 weeks, indicating that superoxide radical participates in the induction of micronuclei and 8-OHdG. In fact, the endogenous superoxide scavenger, Cu/Zn superoxide dismutase, was significantly reduced in the bone marrow cells of rats fed with a Zn-deficient diet for 6 weeks when compared to those of rats fed with a standard diet for 6 weeks (p < 0.005). These observations demonstrate that Zn deficiency elevates the frequency of micronuclei and the induction of 8-OHdG through an increase in the biological action of the superoxide radical. This suggests an increase in carcinogenic initiation resulting from Zn deficiency-induced oxidative stress.
本研究旨在探讨缺锌是否会增加微核的频率，微核是染色体畸变的指标，以及氧化应激导致的细胞 DNA 损伤标志物 8-羟基-2'-脱氧鸟苷（8-OHdG）的诱导。与标准饮食相比，缺锌 6 周的大鼠骨髓细胞中微核频率和 8-OHdG 的诱导均显著增加（p<0.005）。在缺锌饮食 6 周的大鼠中添加标准饮食中的锌 4 周，可将增强的微核和 8-OHdG 的诱导恢复至与标准饮食 10 周的大鼠相当的水平，表明体内缺锌参与了微核和 8-OHdG 的诱导。同样，膜通透性超氧化物歧化酶模拟物超氧化物清除剂 4-羟基-2,2,6,6-四甲基哌啶-1-氧自由基（100 μmol/kg，每天两次）在饮食治疗结束前 10 天处理可将缺锌饮食 6 周的大鼠中微核和 8-OHdG 的诱导降低至与缺锌饮食 6 周的大鼠相当的水平，标准饮食，表明超氧自由基参与了微核和 8-OHdG 的诱导。事实上，与标准饮食 6 周的大鼠相比，缺锌饮食 6 周的大鼠骨髓细胞中的内源性超氧化物清除剂 Cu/Zn 超氧化物歧化酶显著减少（p<0.005）。这些观察结果表明，缺锌通过增加超氧自由基的生物学作用来提高微核的频率和 8-OHdG 的诱导。这表明由于缺锌诱导的氧化应激，致癌起始增加。
