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 H(2)O(2) (75microM) and quercetin (25-100microM) treatment. Analytic detection of iron in cell cultures, treated with 250microM Fe-NTA for 15 min to 24h, showed that 48.02+/-5.14 to 68.31+/-2.11% were rapidly absorbed and then detectable in the cellular fraction. Fe-NTA (250-1000microM) induced DNA breaks and oxidised bases, which were enhanced by subsequent H(2)O(2) exposure. Simultaneous incubation of HT29 clone 19A cells with Fe-NTA and H(2)O(2) for 15 min, 37 degrees C did not change the effect of H(2)O(2) alone. The impact of Fe-NTA and H(2)O(2)-induced oxidative damage is reduced by the antioxidant quercetin (75-67% of H(2)O(2)-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.
Glei
Michael
M
Department of Nutritional Toxicology, Institute of Nutrition, Friedrich-Schiller-University, Dornburger Street 25, 07743 Jena, Germany.
Latunde-Dada
Gladys O
GO
Klinder
Annett
A
Becker
Thomas W
TW
Hermann
Uta
U
Voigt
Klaus
K
Pool-Zobel
Beatrice L
BL
D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000187:drug effects*; D005290:Ferric Compounds / Q000633:toxicity*; D019073:HT29 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D019190:Iron Overload / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D011794:Quercetin / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
D004273:DNA, Neoplasm; D005290:Ferric Compounds; D017382:Reactive Oxygen Species; D011794:Quercetin; D006861:Hydrogen Peroxide