Iron-overload induces oxidative DNA damage in the human colon carcinoma cell line HT29 clone 19A

Dietary iron may contribute to colon cancer risk via production of reactive oxygen species (ROS), The aim of the study was to determine whether physiological ferric/ferrous iron induces oxidative DNA damage in human colon cells. Therefore, differentiated human colon tumour cells (HT29 clone 19A) were incubated with ferric-nitrilotriacetate (Fe-NTA) or with haemoglobin and DNA breaks and oxidised bases were determined by microgelelectrophoresis. The effects of Fe-NTA were measured with additional H2O2 (75 muM) and quercetin (25-100 muM) treatment. Analytic detection of iron in cell cultures, treated with 250 muM Fe-NTA for 15 min to 24 h, showed that 48.02 +/- 5.14 to 68.31 +/- 2.11% were rapidly absorbed and then detectable in the cellular fraction. Fe-NTA (250-1000 muM) induced DNA breaks and oxidised bases, which were enhanced by subsequent H2O2 exposure. Simultaneous incubation of HT29 clone 19A cells with Fe-NTA and H2O2 for 15 min, 37 degreesC did not change the effect of H2O2 alone. The impact of Fe-NTA and H2O2-induced oxidative damage is reduced by the antioxidant quercetin (75-67% of H2O2-control). Haemoglobin was as effective as Fe-NTA in inducing DNA damage. From these results we can conclude that iron is taken up by human colon cells and participates in the induction of oxidative DNA damage. Thus, iron or its capacity to catalyse ROS-formation, is an important colon cancer risk factor. Inhibition of damage by quercetin reflects the potential of antioxidative compounds to influence this risk factor. Quantitative data on the genotoxic impact of ferrous iron (e.g. from red meat) relative to the concentrations of antioxidants (from plant foods) in the gut are now needed to determine the optimal balance of food intake that will reduce exposure to this type of colon cancer risk factor. (C) 2002 Elsevier Science B.V. All rights reserved.