Effect of copper deficiency on oxidative DNA damage in Jurkat T-lymphocytes.
The micronutrient copper is a catalytic cofactor for copper, zinc superoxide dismutase and ceruloplasmin, which are two important antioxidant enzymes. As such, a lack of copper may promote oxidative stress and damage. The purpose of this study was to determine the effect of copper deficiency on oxidative damage to DNA in Jurkat T-lymphocytes. To induce copper deficiency, cells were incubated for 48 h with 5-20 microM 2,3,2-tetraamine (2,3,2-tet), a high affinity copper chelator. Such treatment did not affect cell proliferation/viability, as assessed by measuring mitochondrial reduction of WST-1 reagent (4-[3-(4-Iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-ben zen e disulfonate). Furthermore, the induction of copper deficiency did not promote oxidative DNA damage as evaluated by the comet assay. Comet scores were 15 +/- 0 and 16 +/- 1 for control and copper-deficient cells, respectively. However, the copper-deficient cells sustained greater oxidative DNA damage than the control cells (comet scores of 175 +/- 15 and 50 +/- 10, respectively) when both were oxidatively challenged with 50 microM hydrogen peroxide (H(2)O(2)). Supplemental copper but not zinc or iron prevented the potentiation of the H(2)O(2)-induced oxidative DNA damage caused by 2,3,2-tet. These data suggest that copper deficiency compromises the antioxidant defense system of cells, thereby increasing their susceptibility to oxidative DNA damage.
Pan
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Graduate Program in Nutrition, University of North Carolina at Greensboro, Greensboro, NC 27402-6170, USA.
Loo
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D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000172:deficiency* / Q000378:metabolism / Q000494:pharmacology; D004249:DNA Damage; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D019169:Jurkat Cells; D018384:Oxidative Stress; D011073:Polyamines / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism
D002614:Chelating Agents; D005609:Free Radicals; D011073:Polyamines; C022177:2,3,2-tetramine; D003300:Copper; D006861:Hydrogen Peroxide