Impact of copper on the induction and repair of oxidative DNA damage, poly(ADP-ribosyl)ation and PARP-1 activity

Copper is an essential trace element involved, among other functions, in enzymatic antioxidative defense systems. However, nonprotein bound copper ions have been shown to generate reactive oxygen species. To gain insight into the discrepancy between the protective properties of copper on the one hand and its toxicity on the other hand, we examined the genotoxic effects of CuSO(4) in cultured human cells. Here we report that copper, at cytotoxic concentrations, induces oxidative DNA base modifications and DNA strand breaks. However, at lower noncytotoxic concentrations, copper inhibits the repair of oxidative DNA damage induced by visible light. As a first mechanistic hint, inhibition of H(2)O(2)-induced poly(ADP-ribosyl)ation was identified in cultured cells and further experiments demonstrated a strong inhibition of the activity of isolated poly(ADP-ribose)polymerase-1 (PARP-1) by copper. Bioavailability studies of copper showed a dose-dependent uptake in cells and pointed out the relevance of the applied concentrations. Taken together, the results indicate that copper, under conditions of either disturbed homeostasis or overload due to high exposure, exerts defined genotoxic effects. Hence, a balance needs to be maintained to ensure sufficient uptake and to prevent overload.     

Effects of single dose and regular intake of green tea (Camellia sinensis) on DNA damage,DNA repair,and heme oxygenase‐1 expression in a randomized controlled human supplementation study

Regular intake of green tea (Camellia sinensis) lowers DNA damage in humans, but molecular mechanisms of genoprotection are not clear. Protection could be via direct antioxidant effects of tea catechins, but, paradoxically, catechins have pro‐oxidant activity in vitro, and it is hypothesized that mechanisms relate to redox‐sensitive cytoprotective adaptations. We investigated this hypothesis, focusing particularly on effects on the DNA repair enzyme human oxoguanine glycosylase 1 (hOGG1), and heme oxygenase‐1, a protein that has antioxidant and anti‐inflammatory effects. A randomized, placebo‐controlled, human supplementation study of crossover design was performed. Subjects (n = 16) took a single dose (200 mL of 1.5%, w/v) and 7‐days of (2 × 200 mL 1%, w/v per day) green tea (with water as control treatment). Lymphocytic DNA damage was ～30% (p < 0.001) lower at 60 and 120 min after the single dose and in fasting samples collected after 7‐day tea supplementation. Lymphocytic hOGG1 activity was higher (p < 0.0001) at 60 and 120 min after tea ingestion. Significant increases (p < 0.0005) were seen in hOGG1 activity and heme oxygenase‐1 after 7 days. Results indicate that molecular triggering of redox‐sensitive cytoprotective adaptations and posttranslational changes affecting hOGG1 occur in vivo in response to both a single dose and regular intake of green tea, and contribute to the observed genoprotective effects of green tea.