ToxSci Advance Access published online on July 13, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfl060
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Institute for Nutrition, Department of Nutritional Toxicology, Friedrich-Schiller-University Jena, Dornburger Str. 25, 07743 Jena, Germany
* To whom correspondence should be addressed. 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 because of 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), in adenoma cells (LT97) and in non-transformed primary colon cells. They 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 (Comet FISH, 24-colour-FISH) were determined. U-NTA inhibited growth of HT29 clone 19A cells (75-2000 µM, 72 h) and increased GSH (125-2000 µM, 24 h). U-NTA was genotoxic (1000 µM, 30 minutes), but did not inhibit the repair of DNA damage caused by hydrogen peroxide (H2O2), 4-hydroxynonenal (HNE) and 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (NOH-PhIP). 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 0.5-2 mM U-NTA increased chromosomal aberrations in chromosomes 5, 12 and 17, which harbour the tumour-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. The authors certify that all research involving human subjects was done under full compliance with all government policies and the Helsinki Declaration.
Received March 24, 2006
Accepted June 28, 2006
Environmental Toxicology
Uranyl Nitrilotriacetate (U-NTA), a Stabilized Salt of Uranium, is Genotoxic in Non-Transformed Human Colon Cells and in the Human Colon Adenoma Cell Line LT97
Y. Knöbel 1,
M. Glei 1,
A. Weise 2,
K. Osswald 1,
A. Schäferhenrich 1,
K. K. Richter 3,
U. Claussen 2,
and
B. L. Pool-Zobel 1 *
2 Institute for Human Genetics and Anthropology, Friedrich-Schiller-University Jena, Kollegiengasse 10, 07743 Jena, Germany
3 Department of General and Visceral Surgery, Friedrich-Schiller-University Jena, Erlanger Allee 101, 07743 Jena, Germany
B. L. Pool-Zobel, E-mail: b8pobe{at}uni-jena.de
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  P. A. Escobar, M. T. Smith, A. Vasishta, A. E. Hubbard, and L. Zhang Leukaemia-specific chromosome damage detected by comet with fluorescence in situ hybridization (comet-FISH) Mutagenesis, September 1, 2007; 22(5): 321 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Thiebault, M. Carriere, S. Milgram, A. Simon, L. Avoscan, and B. Gouget Uranium Induces Apoptosis and Is Genotoxic to Normal Rat Kidney (NRK-52E) Proximal Cells Toxicol. Sci., August 1, 2007; 98(2): 479 - 487. [Abstract] [Full Text] [PDF]
|
|