TY - JOUR
T1 - A mouse kidney cell line with a G:C → C:G transversion mutator phenotype
AU - Shin, Chi Y.
AU - Ponomareva, Olga N.
AU - Connolly, Lanelle
AU - Turker, Mitchell S.
N1 - Funding Information:
This work was supported by NIH grants CA56383 and CA76528 (MST). Chi Shin was supported by a training core from NIEHS 1P42 ES10338. We thank Drs. Mike Liskay, Andrew Beurmeyer, and Isabel Mellon for helpful suggestions and Mike Lasarev for help with statistical analysis.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - DNA mismatch repair
KW - Drug resistance
KW - Mutator phenotype
KW - Transversion mutation
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U2 - 10.1016/S0027-5107(02)00073-8
DO - 10.1016/S0027-5107(02)00073-8
M3 - Article
C2 - 12052505
AN - SCOPUS:0037134761
SN - 0027-5107
VL - 503
SP - 69
EP - 76
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
IS - 1-2
ER -