title: Genotoxic effects of two-generational selenium deficiency in mouse somatic and testicular cells.
abstract: Many studies have investigated genotoxic effects of high Se diets but very few have addressed the genotoxicity of Se deprivation and its consequences in germ cells and none in somatic cells. To address these data gaps, C57BL/6 male mice were subjected to Se deprivation starting in the parental generation, i.e. before conception. Mice were given a diet of either low (0.01mg Se/kg diet) or normal (0.23mg Se/kg diet) Se content. Ogg1-deficient (Ogg1 (-/-) ) mice were used as a sensitive model towards oxidative stress due to their reduced capacity to repair oxidised purines. Ogg1 (-/-) mice also mimic the repair characteristics of human post-meiotic male germ cells which have a reduced ability to repair such lesions. The genotoxicity of Se deficiency was addressed by measuring DNA lesions with the alkaline single cell gel electrophoresis (+ Fpg to detect oxidised DNA lesions) in somatic cells (nucleated blood cells and lung cells) and male germ cells (testicular cells). Total Se concentration in liver and GPx activity in plasma and testicular cells were measured. Gene mutation was evaluated by an erythrocyte-based Pig-a assay. We found that Se deprivation of F1 from their conception and until early adulthood led to the induction of DNA lesions in testicular and lung cells expressed as significantly increased levels of DNA lesions, irrespective of the mouse genotype. In blood cells, Se levels did not appear to affect DNA lesions or mutant cell frequencies. The results suggest that the testis was the most sensitive tissue. Thus, genotoxicity induced by the low Se diet in the spermatozoal genome has potential implications for the offspring.
authors.affiliation: Department of Chemicals and Radiation, National Institute of Public Health, Oslo 0456, Norway, Department of Plant and Environmental Sciences, University of Life Sciences, Aas 1430, Norway, and Litron Laboratories, Rochester, NY 14623, USA.
authors.forename: Anne
authors.initials: A
authors.lastname: Graupner
authors.affiliation: Department of Chemicals and Radiation, National Institute of Public Health, Oslo 0456, Norway, Department of Plant and Environmental Sciences, University of Life Sciences, Aas 1430, Norway, and Litron Laboratories, Rochester, NY 14623, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Instanes
authors.affiliation: Department of Chemicals and Radiation, National Institute of Public Health, Oslo 0456, Norway, Department of Plant and Environmental Sciences, University of Life Sciences, Aas 1430, Norway, and Litron Laboratories, Rochester, NY 14623, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Andersen
authors.affiliation: Department of Plant and Environmental Sciences, University of Life Sciences, Aas 1430, Norway, and.
authors.forename: Anicke
authors.initials: A
authors.lastname: Brandt-Kjelsen
authors.affiliation: Litron Laboratories, Rochester, NY 14623, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Dertinger
authors.affiliation: Department of Plant and Environmental Sciences, University of Life Sciences, Aas 1430, Norway, and.
authors.forename: Brit
authors.initials: B
authors.lastname: Salbu
authors.affiliation: Department of Chemicals and Radiation, National Institute of Public Health, Oslo 0456, Norway, Department of Plant and Environmental Sciences, University of Life Sciences, Aas 1430, Norway, and Litron Laboratories, Rochester, NY 14623, USA.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Brunborg
authors.affiliation: Department of Chemicals and Radiation, National Institute of Public Health, Oslo 0456, Norway, Department of Plant and Environmental Sciences, University of Life Sciences, Aas 1430, Norway, and Litron Laboratories, Rochester, NY 14623, USA. ann.karin.olsen@fhi.no.
authors.forename: Ann-Karin
authors.initials: AK
authors.lastname: Olsen
mesh_terms: D000818:Animals; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D005979:Glutathione Peroxidase / Q000032:analysis; D007962:Leukocytes; D008168:Lung / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D018384:Oxidative Stress; D012643:Selenium / Q000032:analysis / Q000172:deficiency*; D013094:Spermatozoa
chemical_list: D005979:Glutathione Peroxidase; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; D012643:Selenium