Maternal Dietary Zinc Influences DNA Strand Break and 8-Hydroxy-2'-Deoxyguanosine Levels in Infant Rhesus Monkey Liver

Abstract

Severe zinc deficiency in rodent models has been shown to influence the frequency of single-strand breaks in DNA isolated from liver. In the current study, we investigated whether DNA isolated from infant monkeys born to mothers fed zinc-restricted diets would be characterized by higher than normal levels of DNA damage. DNA was isolated from 30-day-old infants born to dams fed low zinc (2 or 4 micrograms Zn/g) or control zinc (50 micrograms Zn/g) diets. The amount of single-strand breaks in liver DNA was significantly higher in the low zinc group than in controls; consistent with the above, there was a trend for higher steady state levels of liver 8-hydroxy-2'-deoxyguanosine in the low zinc group. While evidence for DNA damage in the low zinc group was obtained, the activities of several antioxidant enzymes were similar between the low zinc and control groups. In summary, infants born to monkeys fed low zinc diets are characterized by evidence of DNA damage shortly after birth; this damage may be due to an increased rate of oxidative damage and/or a reduction in the rate of DNA repair.

Zinc deficiency, DNA damage and cancer risk

“…Increased oxidant production has been shown in cell cultures grown in zinc-deficient media [18]. In vivo, increases in oxidative protein and DNA damage has been shown in zinc-deficient rats [10,[19][20][21][22]. Zinc deficiency also increases the susceptibility to oxidative injury.…”

Dietary zinc restriction in rats alters antioxidant status and increases plasma F2 isoprostanes

“…A significant proportion of North Americans do not ingest adequate zinc [3]. Based on the 2000-2001 NHANES data, approximately 12% of Americans do not consume the estimated average requirement for zinc and could be at risk for zinc deficiency [4].…”

Dietary zinc restriction and repletion affects DNA integrity in healthy men

“…Our data support the notion that functional consequences of zinc deficiency occur before plasma zinc concentrations decline and highlight the essential role of zinc for maintaining DNA integrity in vivo. Previous studies, using in vitro and in vivo animal models, found that zinc deficiency increased DNA damage in liver or testes (17,18,21,22). To our knowledge, our study is the first report of zinc-related DNA damage in peripheral blood cells of humans.…”

“…Overall, zinc deficiency may both increase oxidative stress and impair DNA integrity, thereby increasing the risk of cancer. In vitro and animal studies have clearly shown increased DNA damage and oxidative stress with zinc deficiency (14)(15)(16)(17)(20)(21)(22). However, the extent to which zinc depletion regulates ox-idative stress and DNA integrity in controlled human studies has yet to be comprehensively explored.…”