title: Comparison of autosomal mutations in mouse kidney epithelial cells exposed to iron ions in situ or in culture.
abstract: Exposure to accelerated iron ions represents a significant health risk in the deep space environment because it induces mutations that can cause cancer. A mutation assay was used to determine the full spectrum of autosomal mutations induced by exposure to 2 Gy of 1 GeV/nucleon iron ions in intact kidney epithelium, and the results were compared with mutations induced in cells of a kidney epithelial cell line exposed in vitro. A molecular analysis for loss of heterozygosity (LOH) for polymorphic loci on chromosome 8, which harbors Aprt, demonstrated iron-ion induction of mitotic recombination, interstitial deletion, and discontinuous LOH events. Iron-ion-induced deletions were detected more readily with the in vitro assay, whereas discontinuous LOH was detected more readily in the intact kidney. The specific induction of discontinuous LOH in vivo suggests that this mutation pattern may serve as an indicator of genomic instability. Interestingly, the frequency of small intragenic events increased as a function of time after exposure, suggesting non-targeted effects. In total, the results demonstrate that 1 GeV/nucleon iron ions can elicit a variety of autosomal mutations and that the cellular microenvironment and the sampling time after exposure can influence the distribution of these mutations in epithelial cell populations.
authors.affiliation: Center for Research on Occupational and Environmental Toxicology (CROET) and, Oregon Health & Science University, Portland, Oregon 97239, USA. turkerm@ohsu.edu
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Turker
authors.forename: Lanelle
authors.initials: L
authors.lastname: Connolly
authors.forename: Cristian
authors.initials: C
authors.lastname: Dan
authors.forename: Michael
authors.initials: M
authors.lastname: Lasarev
authors.forename: Stacey
authors.initials: S
authors.lastname: Gauny
authors.forename: Ely
authors.initials: E
authors.lastname: Kwoh
authors.forename: Amy
authors.initials: A
authors.lastname: Kronenberg
mesh_terms: D000818:Animals; D002460:Cell Line; D002874:Chromosome Mapping; D004847:Epithelial Cells / Q000528:radiation effects; D007504:Iron Radioisotopes / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology / Q000528:radiation effects*; D019656:Loss of Heterozygosity; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction
chemical_list: D007504:Iron Radioisotopes