Iron / genotoxic potential

Ferric iron is genotoxic in non-transformed and preneoplastic human
colon cells.
Knöbel Y, Weise A, Glei M, Sendt W, Claussen U, Pool-Zobel BL
Food Chem Toxicol. 2006 Nov 7;

Iron could be a relevant risk factor for carcinogenesis since it
catalyses the formation of reactive oxygen species (ROS), which damage
DNA. We previously demonstrated genotoxic effects by ferric iron using
the human colon cancer cell line HT29. Here we investigated ferric iron
in primary non-transformed colon cells and in a preneoplastic colon
adenoma cell line (LT97), which both are suitable models to study
effects of carcinogens during early stages of cell transformation.
Genetic damage was determined using the Comet assay. Comet FISH
(fluorescence in situ hybridization) was used to assess specific
effects on TP53. Fe-NTA (0-1000muM, 30min, 37 degrees C) significantly
induced single strand breaks in primary colon cells (500muM Fe-NTA:
Tail intensity [TI] 22.6%+/-5.0% versus RPMI control: TI 10.6%+/-3.9%,
p<0.01) and in LT97 cells (1000muM Fe-NTA: TI 26.8%+/-7.3% versus RPMI
control: TI 11.1%+/-3.7%, p<0.01). With the Comet FISH protocol lower
concentrations of Fe-NTA significantly increased DNA damage already at
100 and 250muM Fe-NTA in primary colon and LT97 adenoma cells,
respectively. This damage was detected as an enhanced migration of TP53
signals into the comet tail in both cell types, which indicates a high
susceptibility of this tumor relevant gene towards Fe-NTA. In
conclusion, Fe-NTA acts genotoxic in non-transformed and in
preneoplastic human colon cells, in which it also enhances migration of
TP53 at relatively low concentrations. Translated to the in vivo
situation these results suggest that iron overload putatively
contributes to a genotoxic risk during early stages of colorectal
carcinogenesis on account of its genotoxic potential in non-tumorigenic
human colon cells.


Abstract · PubMed FullText · SFX · GS Clip Export InterDB ·
Terms Related · Graph Tag · Scopus · Cites
10.1016/j.fct.2006.10.028


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