PMID- 17157427
OWN - NLM
STAT- MEDLINE
DCOM- 20070522
LR  - 20121115
IS  - 0278-6915 (Print)
IS  - 0278-6915 (Linking)
VI  - 45
IP  - 5
DP  - 2007 May
TI  - Ferric iron is genotoxic in non-transformed and preneoplastic human colon cells.
PG  - 804-11
AB  - 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 (0-1000 microM, 30 min, 37 degrees C) significantly induced single strand 
      breaks in primary colon cells (500 microM Fe-NTA: Tail intensity [TI] 
      22.6%+/-5.0% versus RPMI control: TI 10.6%+/-3.9%, p<0.01) and in LT97 cells 
      (1000 microM 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 250 microM 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.
FAU - Knobel, Y
AU  - Knobel Y
AD  - Institute of Nutrition, Department of Nutritional Toxicology, 
      Friedrich-Schiller-University, Dornburger Str. 25, 07743 Jena, Germany.
FAU - Weise, A
AU  - Weise A
FAU - Glei, M
AU  - Glei M
FAU - Sendt, W
AU  - Sendt W
FAU - Claussen, U
AU  - Claussen U
FAU - Pool-Zobel, B L
AU  - Pool-Zobel BL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20061107
PL  - England
TA  - Food Chem Toxicol
JT  - Food and chemical toxicology : an international journal published for the British 
      Industrial Biological Research Association
JID - 8207483
RN  - 0 (Ferric Compounds)
RN  - 0 (Nitrates)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - N8H8402XOB (ferric nitrate)
SB  - IM
MH  - Adenoma/genetics/pathology
MH  - Cell Line, Tumor
MH  - Chromosome Aberrations
MH  - Colon/*drug effects
MH  - Colonic Neoplasms/genetics/pathology
MH  - Comet Assay
MH  - DNA Damage/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Ferric Compounds/*toxicity
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Nitrates/*toxicity
MH  - Reactive Oxygen Species/metabolism
MH  - Tumor Suppressor Protein p53/analysis
EDAT- 2006/12/13 09:00
MHDA- 2007/05/23 09:00
CRDT- 2006/12/13 09:00
PHST- 2005/11/15 00:00 [received]
PHST- 2006/10/09 00:00 [revised]
PHST- 2006/10/30 00:00 [accepted]
PHST- 2006/12/13 09:00 [pubmed]
PHST- 2007/05/23 09:00 [medline]
PHST- 2006/12/13 09:00 [entrez]
AID - S0278-6915(06)00317-6 [pii]
AID - 10.1016/j.fct.2006.10.028 [doi]
PST - ppublish
SO  - Food Chem Toxicol. 2007 May;45(5):804-11. doi: 10.1016/j.fct.2006.10.028. Epub 
      2006 Nov 7.