Effects of zinc deficiency on DNA damage, oxidative stress and oxidant defense in peripheral blood of rats

Abstract

Approximately 12% of Americans do not consume the EAR for zinc and could be at risk for marginal zinc deficiency. There is accumulating evidence that zinc deficiency is associated with increased risk of cancer mortality and increased DNA damage in vitro. We hypothesize that zinc deficiency in vivo causes DNA damage through increases in oxidative stress and compromised oxidant defense. To test this hypothesis, SD rats were fed an adequate zinc diet (MZA 30ppm) or marginal zinc deficient diet (MZD 6ppm) for 6 weeks. Comet assay revealed a significant increase in DNA damage in peripheral blood cells of MZD rats. Oxidative stress was also increased as indicated by alterations in plasma F2‐isoprostanes. However, no changes in plasma total antioxidant capacity, ascorbic acid, α–tocopherol, and erythrocyte SOD activity were found with MZD. We also investigated the effects of severe zinc deficiency with repletion on DNA damage. Rats were fed an adequate zinc (30ppm), zinc deficient (<1ppm), or pair‐fed diet for 3 weeks prior to 1 week zinc repletion. DNA damage of peripheral blood cells was significantly increased after zinc depletion, but reversed back to normal levels after zinc repletion. These data suggest interactions among zinc deficiency, DNA integrity and oxidative stress and implicate the role of zinc deficiency in cancer susceptibility.