A mouse kidney cell line with a G: C → C:G transversion mutator phenotype

Chi Y. Shin, Olga N. Ponomareva, Lanelle Connolly, Mitchell Turker

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)69-76
Number of pages8
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume503
Issue number1-2
StatePublished - Jun 19 2002

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Thioguanine
Methylnitronitrosoguanidine
Phenotype
Kidney
Cell Line
Cisplatin
Null Lymphocytes
Microsatellite Instability
Mutagens
Ionizing Radiation
Hydrogen Peroxide
Epithelial Cells
Radiation
Mutation
Turcot syndrome
Radiation Exposure

Keywords

  • DNA mismatch repair
  • Drug resistance
  • Mutator phenotype
  • Transversion mutation

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

Cite this

A mouse kidney cell line with a G : C → C:G transversion mutator phenotype. / Shin, Chi Y.; Ponomareva, Olga N.; Connolly, Lanelle; Turker, Mitchell.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 503, No. 1-2, 19.06.2002, p. 69-76.

Research output: Contribution to journalArticle

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