Influence of iron-overload on DNA damage and its repair in human leukocytes in vitro

Abstract

Iron is an important element that modulates the production of reactive oxygen species, which are thought to play a causative role in biological processes such as mutagenesis and carcinogenesis. The potential genotoxicity of dietary iron has been seldom studied in human leukocyte and only few reports have investigated in human colon tumor cells. Therefore, DNA damage and repair capacity of human leukocytes were examined using comet assay for screening the potential toxicity of various iron-overloads such as ferric-nitrilotriacetate (Fe-NTA), FeSO 4, hemoglobin and myoglobin, and compared with 200 μM of H 2O 2 and HNE. The iron-overloads tested were not cytotoxic in the range of 10–1000 μM by trypan blue exclusion assay. The exposure of leukocytes to Fe-NTA (500 and 1000 μM), FeSO 4 (250–1000 μM), hemoglobin (10 μM) and myoglobin (250 μM) for 30 min induced significantly higher DNA damage than NC. Treatment with 500 and 1000 μM of Fe-NTA showed a similar genotoxic effect to H 2O 2, and a significant higher genotoxic effect than HNE. The genotoxicity of FeSO 4 (250–1000 μM), hemoglobin (10 μM) and myoglobin (250 μM) was not significantly different from that of H 2O 2 and HNE. Iron-overloads generated DNA strand break were rejoined from the first 1 h. Their genotoxic effect was not observed at 24 h. These data from this study provide additional information on the genotoxicity of iron-overloads and self-repair capacity in human leukocytes.