title: A cell line selected for resistance to ionizing radiation exhibits cross resistance to other genotoxic agents and a mutator phenotype for loss of heterozygosity events.
abstract: An ionizing radiation resistant derivative was obtained from the mouse P19H22 (aprt hemizygote) embryonal carcinoma cell line by repeated exposure to 137Cs gamma radiation. Ionizing radiation resistance in the 6Gy-R cell line was not correlated with a failure to undergo cell cycle arrest or a loss of the p53 response after exposure to 137Cs gamma radiation. Moreover, the cells did not display increased resistance to bleomycin, a double strand break inducing agent. However, the cells did display increased resistance to ultraviolet radiation, ethyl methanesulfonate, and 95% oxygen. A mutational analysis demonstrated a > 700 fold-fold increase in the frequency of aprt mutants for the 6Gy-R cells, but no change in the frequency of hprt or dhfr mutants. A molecular analysis suggested that the aprt mutations in the 6Gy-R cells arose by recombinational events. A possible association between radiation resistance, DNA repair, and a mutator phenotype for large-scale mutational events is discussed.
authors.affiliation: Department of Pathology, University of Kentucky, Lexington 40536, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Walker
authors.forename: C D
authors.initials: CD
authors.lastname: Jennings
authors.forename: J
authors.initials: J
authors.lastname: Pulliam
authors.forename: C
authors.initials: C
authors.lastname: Ogburn
authors.forename: G M
authors.initials: GM
authors.lastname: Martin
authors.forename: M
authors.initials: M
authors.lastname: Urano
authors.forename: M S
authors.initials: MS
authors.lastname: Turker
mesh_terms: D000228:Adenine Phosphoribosyltransferase / Q000737:chemistry / Q000235:genetics / Q000528:radiation effects; D000818:Animals; D018236:Carcinoma, Embryonal / Q000201:enzymology / Q000235:genetics*; D002588:Cesium Radioisotopes; D002898:Chromosomes, Human, Pair 8 / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D002999:Clone Cells; D005720:Gamma Rays; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics / Q000528:radiation effects; D019656:Loss of Heterozygosity / Q000187:drug effects / Q000528:radiation effects*; D051379:Mice; D009153:Mutagens / Q000528:radiation effects; D010641:Phenotype; D011836:Radiation Tolerance / Q000187:drug effects*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics / Q000528:radiation effects; D014407:Tumor Cells, Cultured
chemical_list: D002588:Cesium Radioisotopes; D009153:Mutagens; D013762:Tetrahydrofolate Dehydrogenase; D000228:Adenine Phosphoribosyltransferase; D007041:Hypoxanthine Phosphoribosyltransferase