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Zinc Deficiency Enhances the Induction of Micronuclei and 8-Hydroxy-2′-Deoxyguanosine Via Superoxide Radical in Bone Marrow of Zinc-Deficient Rats

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Abstract

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.

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Acknowledgments

This work was supported by grants (no. 21590715) for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. 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

    Ichiro Kawasaki, Yuji Suzuki & Hiroyuki Yanagisawa

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  1. Ichiro Kawasaki
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  2. Yuji Suzuki
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  3. Hiroyuki Yanagisawa
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Correspondence to Hiroyuki Yanagisawa.

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Kawasaki, I., Suzuki, Y. & Yanagisawa, H. Zinc Deficiency Enhances the Induction of Micronuclei and 8-Hydroxy-2′-Deoxyguanosine Via Superoxide Radical in Bone Marrow of Zinc-Deficient Rats. Biol Trace Elem Res 154, 120–126 (2013). https://doi.org/10.1007/s12011-013-9706-8

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  • DOI: https://doi.org/10.1007/s12011-013-9706-8

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