Zinc and genomic stability.

Zinc (Zn) is an essential trace element required for both optimal human health and maintaining genomic stability. The main aim of this thesis was to address important knowledge gaps regarding the possible impact of Zn status on genomic stability events in both lymphocytes and epithelial cells using both in vitro and in vivo models. The project also aimed to study the differential impact of Zn Carnosine (ZnC) and Zn Sulphate (ZnSO₄) on genome stability as the former is a newly emerging commercially available supplement renown for its antioxidant capacity. The in vitro studies investigated the effects of ZnSO₄ and ZnC on cell proliferation via MTT assay and DNA damage rates and was measured using both the comet assay and the Cytokinesis-block micronucleus cytome (CBMN-Cyt) assay in the WIL2-NS human lymphoblastoid cell line and HOK cell line. This study also investigated the impact of Zn status on both telomere length and telomere base damage in vitro. An in vivo study was designed to further investigate the effect of Zn supplementation in minimising genome instability events in lymphocytes. An increased intake of Zn may reduce the risk of degenerative diseases but may be toxic if taken in excess. This study aimed to investigate whether taking daily supplements of 20 mg of Zn as Zn Carnosine can improve Zn status, genome stability events and Zn transporter genes in an elderly South Australian cohort characterised by having low plasma Zn levels. In conclusion, the in vitro studies suggest that 1) Zn deficiency (0 μM) and high Zn concentrations increase DNA damage; 2) Zn at 4-16 μM is optimal in maintaining genome stability events; 3) Zn at 16-32 μM is optimal in protecting the cell against DNA damage induced by irradiation and hydrogen peroxide challenges; and 4) Zn may play an important role in telomere maintenances. The in vivo study suggests that Zn supplementation may be beneficial in an elderly population with marginal lowered Zn status by raising plasma Zn levels, lowering DNA damage events and modifies Zn transporter gene expression.Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 201