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 200μM of H(2)O(2) and HNE. The iron-overloads tested were not cytotoxic in the range of 10-1000 microM by trypan blue exclusion assay. The exposure of leukocytes to Fe-NTA (500 and 1000 microM), FeSO(4) (250-1000 microM), hemoglobin (10 microM) and myoglobin (250 microM) for 30 min induced significantly higher DNA damage than NC. Treatment with 500 and 1000 microM of Fe-NTA showed a similar genotoxic effect to H(2)O(2), and a significant higher genotoxic effect than HNE. The genotoxicity of FeSO(4) (250-1000 microM), hemoglobin (10 microM) and myoglobin (250 microM) was not significantly different from that of H(2)O(2) and HNE. Iron-overloads generated DNA strand break were rejoined from the first 1h. Their genotoxic effect was not observed at 24h. These data from this study provide additional information on the genotoxicity of iron-overloads and self-repair capacity in human leukocytes.

• Authors: Jae-Hee Park, Eunju Park
• Journal: Mutation research (Mutat Res) Vol. 718 Issue 1-2 Pg. 56-61 (Jan 10 2011) ISSN: 0027-5107 [Print] Netherlands
• PMID: 20974287 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2010 Elsevier B.V. All rights reserved.

Chemical References

• Ferric Compounds
• Hemoglobins
• Mutagens
• Myoglobin
• ferric sulfate
• Nitrilotriacetic Acid
• ferric nitrilotriacetate

Topics

• Cell Survival (drug effects)
• Comet Assay
• DNA Damage
• DNA Repair
• Ferric Compounds (toxicity)
• Hemoglobins (toxicity)
• Humans
• In Vitro Techniques
• Iron Overload (genetics, metabolism)
• Leukocytes (cytology, drug effects, metabolism)
• Mutagens (toxicity)
• Myoglobin (toxicity)
• Nitrilotriacetic Acid (analogs & derivatives, toxicity)
• Oxidative Stress (drug effects)