Spontaneously immortalized cell lines obtained from adult Atm null mice retain sensitivity to ionizing radiation and exhibit a mutational pattern suggestive of oxidative stress

Blythe M. Gage, Daniel Alroy, Chi Y. Shin, Olga N. Ponomareva, Sonu Dhar, Girdhar G. Sharma, Tej K. Pandita, Mathew J. Thayer, Mitchell S. Turker

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The study of Ataxia-telangiectasia (A-T) has benefited significantly from mouse models with knockout mutations for the Atm (A-T mutation) locus. While these models have proven useful for in vivo studies, cell cultures from Atm null embryos have been reported to grow poorly and then senesce. In this study, we initiated primary cultures from adult ears and kidneys of Atm homozygous mice and found that these cultures immortalized readily without loss of sensitivity to ionizing radiation and other Atm related cell cycle defects. A mutational analysis for loss of expression of an autosomal locus showed that ionizing radiation had a mutagenic effect. Interestingly, some spontaneous mutants exhibited a mutational pattern that is characteristic of oxidative mutagenesis. This result is consistent with chronic oxidative stress in Atm null cells. In total, the results demonstrate that permanent cell lines can be established from the tissues of adult mice homozygous for Atm and that these cell fines will exhibit expected and novel consequences of this deficiency.

Original languageEnglish (US)
Pages (from-to)4291-4297
Number of pages7
JournalOncogene
Volume20
Issue number32
DOIs
StatePublished - Jul 19 2001

Keywords

  • Immortalized Atm null cells
  • Ionizing radiation
  • Mutagenesis oxidative stress

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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