The function of zinc in the maintenance of DNA integrity in vivo
In rats, severe zinc-depletion caused an increase in DNA damage in peripheral blood cells that decreased following zinc-repletion. DNA repair functions were impaired as indicated by compromised p53 DNA binding and differential activation of DNA repair proteins. Importantly, marginal zinc-depletion (MZD) also increased DNA damage and oxidative stress, and impaired DNA repair functions. However, these effects were not observed in the prostate. Only in combination with an exogenous stress (exercise), MZD increased DNA damage in the prostate, indicating that MZD may sensitize the prostate to exogenous DNA damaging agents.
Similar to the rat study, marginal dietary zinc depletion (6wk) in healthy males increased DNA strand breaks in peripheral blood cells, alterations which were ameliorated by zinc repletion (4wk). Oxidative stress and antioxidants were not altered during zinc depletion/repletion periods.
The increases in DNA damage were associated with impaired zinc homeostasis. MZD decreased zinc concentration as well as ZnT2 expression in the prostate dorsolateral lobe, indicating disregulation of zinc transporter and zinc homeostasis.
Taken together, these studies suggest a key function of zinc in maintaining DNA integrity. Thus, the maintenance of adequate dietary zinc may have an important impact on protecting tissues, such as the prostate, from DNA damage and decreasing cancer risk.
Advisor:Ho, Emily; Traber, Maret G; Tammy, Bray M; Turner, Russell T; Hall, Jean A
School:Oregon State University
School Location:USA - Oregon
Source Type:Master's Thesis
Keywords:dna damage zinc deficiency repair oxidative stress prostate cancer men s health diseases nutritional aspects in the body
Date of Publication:05/07/2009