Induction of micronuclei by zinc in human leukocytes: a study using cytokinesis-block micronucleus assay.
ABSTRACT In the present study, we report the results of the capability of zinc chloride for the induction of micronuclei in cultured human leukocytes using cytokinesis-block micronucleus assay. Two concentrations of zinc chloride (1.5 x 10(-4) M and 3.0 x 10(-4) M) were used to evaluate the potential of this zinc salt to induce micronucleus formation. This effect was compared with positive (mitomycin C treated) and negative controls (no salt added). Our results show a significant (p < or = 0.001) increase of micronucleated cytokinesis-blocked cells (MNCBs) in zinc-chloride-treated cells compared to the negative control. Induction of MNCBs was not in a dose-dependent manner for zinc chloride concentrations tested. This report is the first to describe the efficiency of cytokinesis-block micronucleus assay to evaluate the genotoxic effects of zinc salt.
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ABSTRACT: Zinc (Zn) is an essential trace element required for maintaining both optimal human health and genomic stability. Zn plays a critical role in the regulation of DNA repair mechanisms, cell proliferation, differentiation and apoptosis involving the action of various transcriptional factors and DNA or RNA polymerases. Zn is an essential cofactor or structural component for important antioxidant defence proteins and DNA repair enzymes such as Cu/Zn SOD, OGG1, APE and PARP and may also affect activities of enzymes such as BHMT and MTR involved in methylation reactions in the folate-methionine cycle. This review focuses on the role of Zn in the maintenance of genome integrity and the effects of deficiency or excess on genomic stability events and cell death.Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 09/2011; 733(1-2):111-21. · 3.90 Impact Factor
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ABSTRACT: Zinc (Zn) is an essential component of Zn-finger proteins and acts as a cofactor for enzymes required for cellular metabolism and in the maintenance of DNA integrity. The study investigated the genotoxic and cytotoxic effects of Zn deficiency or excess in a primary human oral keratinocyte cell line and determined the optimal concentration of two Zn compounds (Zn Sulphate (ZnSO(4)) and Zn Carnosine (ZnC)) to minimise DNA damage. Zn-deficient medium (0 μM) was produced using Chelex treatment, and the two Zn compounds ZnSO(4) and ZnC were tested at concentrations of 0.0, 0.4, 4.0, 16.0, 32.0 and 100.0 μM. Cell viability was decreased in Zn-depleted cells (0 μM) as well as at 32 μM and 100 μM for both Zn compounds (P < 0.0001) as measured via the MTT assay. DNA strand breaks, as measured by the comet assay, were found to be increased in Zn-depleted cells compared with the other treatment groups (P < 0.05). The Cytokinesis Block Micronucleus Cytome assay showed a significant increase in the frequency of both apoptotic and necrotic cells under Zn-deficient conditions (P < 0.05). Furthermore, elevated frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBuds) were observed at 0 and 0.4 μM Zn, whereas these biomarkers were minimised for both Zn compounds at 4 and 16 μM Zn (P < 0.05), suggesting these concentrations are optimal to maintain genome stability. Expression of PARP, p53 and OGG1 measured by western blotting was increased in Zn-depleted cells indicating that DNA repair mechanisms are activated. These results suggest that maintaining Zn concentrations within the range of 4-16 μM is essential for DNA damage prevention in cultured human oral keratinocytes.Genes & Nutrition 09/2011; 7(2):139-54. · 3.33 Impact Factor