Serum zinc concentrations correlate with DNA strand break biomarkers in two historical mining communities

Zinc plays an essential role in human health and protects against genotoxicity through its functions in antioxidant defense and DNA damage repair pathways. Human clinical trials have found that zinc supplementation decreases DNA strand breaks, whereas dietary zinc depletion is associated with increased DNA strand breaks that are alleviated by zinc repletion. However, there is limited information on the relationship between serum zinc concentrations and biomarkers of DNA damage in human populations that are not defined as zinc deficient. We hypothesized that there is an inverse relationship between serum zinc concentrations and DNA damage biomarkers in two populations subject to complex environmental exposures. We compared three zinc-sensitive biomarkers of DNA damage: DNA strand breaks (Comet assay), oxidative DNA damage (8‑hydroxy-2-deoxyguanosine, 8-OHdG), and poly(ADP-ribose) polymerase (PARP) activity. We found that serum zinc concentrations below the World Health Organization's recommended value for zinc adequacy were detected in 21% and 51% of the Cheyenne River Sioux Tribe (CRST) and Navajo Birth Cohort Study (NBCS) cohorts, respectively. The degree of heterogeneity in serum zinc concentrations between the two cohorts was determined through pseudo-intervention analysis. A statistical meta-analysis using a random-effects model to account for cohort heterogeneity demonstrated reduced DNA strand breaks, but not oxidative DNA damage, with higher serum zinc concentrations. We conclude that serum zinc is an important determinant of DNA damage in human populations and that DNA damage biomarkers are not equivalent for detecting the impact of zinc on DNA damage.