title: Uranyl nitrilotriacetate, a stabilized salt of uranium, is genotoxic in nontransformed human colon cells and in the human colon adenoma cell line LT97.
abstract: 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.
authors.affiliation: Department of Nutritional Toxicology, Institute for Nutrition, Institute for Human Genetics and Anthropology, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
authors.forename: Yuonne
authors.initials: Y
authors.lastname: Knöbel
authors.forename: Michael
authors.initials: M
authors.lastname: Glei
authors.forename: Anja
authors.initials: A
authors.lastname: Weise
authors.forename: Kerstin
authors.initials: K
authors.lastname: Osswald
authors.forename: Anja
authors.initials: A
authors.lastname: Schäferhenrich
authors.forename: Konrad Klaus
authors.initials: KK
authors.lastname: Richter
authors.forename: Uwe
authors.initials: U
authors.lastname: Claussen
authors.forename: Beatrice Louise
authors.initials: BL
authors.lastname: Pool-Zobel
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002869:Chromosome Aberrations; D003106:Colon / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D004249:DNA Damage; D005978:Glutathione / Q000032:analysis; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D014501:Uranium / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D014501:Uranium; D005978:Glutathione