PMID- 16840563
OWN - NLM
STAT- MEDLINE
DCOM- 20061026
LR  - 20131121
IS  - 1096-6080 (Print)
IS  - 1096-0929 (Linking)
VI  - 93
IP  - 2
DP  - 2006 Oct
TI  - Uranyl nitrilotriacetate, a stabilized salt of uranium, is genotoxic in 
      nontransformed human colon cells and in the human colon adenoma cell line LT97.
PG  - 286-97
AB  - Previous uranium mining in the "Wismut" region in Germany enhanced environmental 
      distribution of heavy metals and radionuclides. Carryover effects may now lead to 
      contamination of locally produced foods. Compounds of "Wismut" origin are 
      probably genotoxic via their irradiating components (radon) or by interacting 
      directly with cellular macromolecules. To assess possible hazards, we 
      investigated the genotoxic effects of uranyl nitrilotriacetate (U-NTA) in human 
      colon tumor cells (HT29 clone 19A), adenoma cells (LT97), and nontransformed 
      primary colon cells. These are target cells of oral exposure to environmentally 
      contaminated foods and represent different cellular stages during colorectal 
      carcinogenesis. Colon cells were incubated with U-NTA. Cell survival, 
      cytotoxicity, cellular glutathione (GSH) levels, genotoxicity, and DNA repair 
      capacity (comet assay), as well as gene- and chromosome-specific damage 
      combination of comet assay and fluorescence in situ hybridization [FISH], 
      24-color FISH) were determined. U-NTA inhibited growth of HT29 clone 19A cells 
      (75-2000 microM, 72 h) and increased GSH (125-2000 microM, 24 h). U-NTA was 
      genotoxic (1000 microM, 30 min) but did not inhibit the repair of DNA damage 
      caused by hydrogen peroxide (H(2)O(2)), 4-hydroxynonenal, and 
      2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]-pyridine. U-NTA was also genotoxic 
      in LT97 cells and primary colon cells, where it additionally increased migration 
      of TP53 into the comet tail. In LT97 cells, 0.5-2mM U-NTA increased chromosomal 
      aberrations in chromosomes 5, 12, and 17, which harbor the tumor-related genes 
      APC, KRAS, and TP53. It may be concluded that uranium compounds could increase 
      alimentary genotoxic exposure in humans if they reach the food chain in 
      sufficient amounts.
FAU - Knobel, Yuonne
AU  - Knobel Y
AD  - Department of Nutritional Toxicology, Institute for Nutrition, Institute for 
      Human Genetics and Anthropology, Friedrich-Schiller-University Jena, 07743 Jena, 
      Germany.
FAU - Glei, Michael
AU  - Glei M
FAU - Weise, Anja
AU  - Weise A
FAU - Osswald, Kerstin
AU  - Osswald K
FAU - Schaferhenrich, Anja
AU  - Schaferhenrich A
FAU - Richter, Konrad Klaus
AU  - Richter KK
FAU - Claussen, Uwe
AU  - Claussen U
FAU - Pool-Zobel, Beatrice Louise
AU  - Pool-Zobel BL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060713
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 4OC371KSTK (Uranium)
RN  - GAN16C9B8O (Glutathione)
SB  - IM
MH  - Adenoma/genetics/pathology
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Chromosome Aberrations
MH  - Colon/*drug effects
MH  - Colonic Neoplasms/genetics/pathology
MH  - DNA Damage
MH  - Glutathione/analysis
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Reactive Oxygen Species
MH  - Tumor Suppressor Protein p53/analysis
MH  - Uranium/*toxicity
EDAT- 2006/07/15 09:00
MHDA- 2006/10/27 09:00
CRDT- 2006/07/15 09:00
PHST- 2006/07/15 09:00 [pubmed]
PHST- 2006/10/27 09:00 [medline]
PHST- 2006/07/15 09:00 [entrez]
AID - kfl060 [pii]
AID - 10.1093/toxsci/kfl060 [doi]
PST - ppublish
SO  - Toxicol Sci. 2006 Oct;93(2):286-97. doi: 10.1093/toxsci/kfl060. Epub 2006 Jul 13.