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.
Original language | English (US) |
---|---|
Pages (from-to) | 69-76 |
Number of pages | 8 |
Journal | Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis |
Volume | 503 |
Issue number | 1-2 |
DOIs | |
State | Published - 2002 |
Keywords
- DNA mismatch repair
- Drug resistance
- Mutator phenotype
- Transversion mutation
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Health, Toxicology and Mutagenesis