title: Low intracellular zinc induces oxidative DNA damage, disrupts p53, NFkappa B, and AP1 DNA binding, and affects DNA repair in a rat glioma cell line.
abstract: Approximately 10% of the U.S. population ingests <50% of the current recommended daily allowance for zinc. We investigate the effect of zinc deficiency on DNA damage, expression of DNA-repair enzymes, and downstream signaling events in a cell-culture model. Low zinc inhibited cell growth of rat glioma C6 cells and increased oxidative stress. Low intracellular zinc increased DNA single-strand breaks (comet assay). Zinc-deficient C6 cells also exhibited an increase in the expression of the zinc-containing DNA-repair proteins p53 and apurinic endonuclease (APE). Repletion with zinc restored cell growth and reversed DNA damage. APE is a multifunctional protein that not only repairs DNA but also controls DNA-binding activity of many transcription factors that may be involved in cancer progression. The ability of the transcription factors p53, nuclear factor kappaB, and activator protein 1 (AP1) to bind to consensus DNA sequences was decreased markedly with zinc deficiency, as assayed by electrophoretic mobility-shift assays. Thus, low intracellular zinc status causes oxidative DNA damage and induces DNA-repair protein expression, but binding of p53 and important downstream signals leading to proper DNA repair are lost without zinc.
authors.affiliation: University of California, Berkeley, CA 94720, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Ho
authors.forename: Bruce N
authors.initials: BN
authors.lastname: Ames
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015032:Zinc / Q000172:deficiency*
chemical_list: D016328:NF-kappa B; D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53; D004247:DNA; D015032:Zinc