title: A mouse kidney cell line with a G:C --> C:G transversion mutator phenotype.
abstract: We report the identification of a mouse kidney epithelial cell line (K435) in which G:C-->C:G transversion mutations occur at an elevated rate and are the predominant spontaneous events observed at the selectable Aprt locus. Of three genotoxins tested, ultraviolet radiation (UV), ionizing radiation, and hydrogen peroxide, only UV exposure was able to alter the spectrum of small mutational events. To determine if the G:C-->C:G mutator phenotype was due to a deficiency in the mismatch repair pathway, the K435 cells were tested for resistance to 6-thioguanine, cisplatin, and MNNG. Although the K435 cells were as resistant to 6-thioguanine and cisplatin as Pms2 and Mlh1 null kidney cells, they were hypersensitive to MNNG. Moreover, the K435 cells do not exhibit microsatellite instability, a hallmark of mismatch repair deficiency. These results suggest that a novel mechanism, which does not include a classical deficiency in mismatch repair, accounts for the G:C-->C:G mutator phenotype.
authors.affiliation: Center for Research on Occupational and Environmental Toxicology, Oregon Health and Sciences University, Portland, OR 97201, USA.
authors.forename: Chi Y
authors.initials: CY
authors.lastname: Shin
authors.forename: Olga N
authors.initials: ON
authors.lastname: Ponomareva
authors.forename: Lanelle
authors.initials: L
authors.lastname: Connolly
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Turker
mesh_terms: D000818:Animals; D020137:Base Pair Mismatch; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology; D004260:DNA Repair / Q000235:genetics*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D051379:Mice; D018895:Microsatellite Repeats; D009154:Mutation; D010641:Phenotype; D013866:Thioguanine / Q000494:pharmacology; D014466:Ultraviolet Rays
chemical_list: D008769:Methylnitronitrosoguanidine; D013866:Thioguanine; D002945:Cisplatin