Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

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

Oncogene volume 20, pages 4291–4297 (2001)Cite this article

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 lines will exhibit expected and novel consequences of this deficiency.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Barlow C, Hirotsune S, Paylor R, Liyanage M, Eckhaus M, Collins F, Shiloh Y, Crawley JN, Ried T, Tagle D, Wynshaw-Boris A . 1996 Cell 86: 159–171

  • Cole J, Arlett CF, Green MHL, Harcourt SA, Priestley A, Henderson L, Cole H, James E, Richmond F . 1988 Int. J. Radiat. Biol. 54: 929–943

  • Cooper GE, DiMartino DL, Turker MS . 1991 Somat. Cell. Mol. Genet. 17: 105–116

  • Cooper GE, Khattar NH, Bishop PL, Turker MS . 1992 Somat. Cell. Mol. Genet. 18: 215–226

  • Dickerman LH, Tischfield JA . 1978 Mutat. Res. 49: 83–94

  • Elson A, Wang Y, Daugherty CJ, Morton CC, Zhou F, Campos-Torres J, Leder P . 1996 Proc. Natl. Acad. Sci. USA 93: 13084–13089

  • Freyer GA, Palmer DA, Yu Y, Miller RC, Pandita TK . 1996 Mutat. Res. 357: 237–244

  • Gatei M, Shkedy D, Khanna KK, Uzeil T, Shiloh Y, Pandita TK, Lavin MF, Rotman G . 2001 Oncogene 20: 289–294

  • Hawley RS, Friend SH . 1996 Genes Dev. 10: 2383–2388

  • Heim RA, Lench NJ, Swift M . 1992 Mutat. Res. 284: 25–36

  • Hoekstra MF . 1997 Curr. Opin. Genet. Dev. 7: 170–175

  • Horn PL, Turker MS, Ogburn CE, Disteche CM, Martin GM . 1984 J. Cell. Physiol. 121: 309–315

  • Khattar NH, Turker MS . 1997 Somat. Cell. Mol. Genet. 23: 51–61

  • Lu X, Lane DP . 1993 Cell 75: 765–778

  • Meyn MS . 1993 Science 260: 1327–1330

  • Meyn MS . 1999 Clin. Genet. 55: 289–304

  • Pandita TK, Geard CR . 1996 Radiat. Res. 145: 730–739

  • Pandita TK, Hall EJ, Hei TK, Piatyszek MA, Wright WE, Piao CQ, Pandita RK, Willey JC, Geard CR, Kastan MB, Shay JW . 1996 Oncogene 13: 1423–1430

  • Pandita TK, Hittelman WN . 1992 Radiat. Res. 131: 214–223

  • Pandita TK, Pathak S, Geard CR . 1995 Cytogenet. Cell Genet. 71: 86–93

  • Reznikoff CA, Bertram JS, Brankow DW, Heidelberger C . 1973a Cancer Res. 33: 3239–3249

  • Reznikoff CA, Brankow DW, Heidelberger C . 1973b Cancer Res. 33: 3231–3238

  • Roscheisen C, Haupter S, Zechner U, Speit G . 1994 Som. Cell. Mol. Gen. 20: 493–504

  • Rose JA, Yates PA, Simpson J, Tischfield JA, Stambrook PJ, Turker MS . 2000 Cancer Res. 60: 3404–3408

  • Rotman G, Shiloh Y . 1997 BioEssays 19: 911–917

  • Shao C, Deng L, Henegariu O, Liang L, Raikwar N, Sahota A, Stambrook PJ, Tischfield JA . 1999 Proc. Natl. Acad. Sci. USA 96: 9230–9235

  • Stambrook PJ, Shao C, Stockelman M, Boivin G, Engle SJ, Tischfield JA . 1996 Environ. Mol. Mutagen. 28: 471–482

  • Turker MS, Gage BM, Rose JA, Elroy D, Ponomareva ON, Stambrook PJ, Tischfield JA . 1999a Cancer Res. 59: 1837–1839

  • Turker MS, Gage BM, Rose JA, Ponomareva ON, Tischfield JA, Stambrook PJ, Barlow C, Wynshaw-Boris A . 1999b Cancer Res. 59: 4781–4783

  • Turker MS, Walker KA, Jennings GD, Mellon I, Yustafji A, Urano M . 1995 Mutat. Res. 329: 97–105

  • Walker KA, Jennings CD, Pulliam J, Ogburn CE, Martin GM, Urano M, Turker MS . 1997 Somat. Cell. Mol. Genet. 23: 111–121

  • Westphal CH, Hoyes KP, Canman CE, Huang X, Kastan MB, Hendry JH, Leder P . 1998 Cancer Res. 58: 5637–5639

  • Wood L, Halvorsen T, Dhar S, Baur J, Wright W, Hande MP, Calaf G, Levine F, Shay JW, Wang J, Pandita TK . 2001 Oncogene 20: 278–288

  • Xu Y, Ashley T, Brainerd EE, Bronson RT, Meyn MS, Baltimore D . 1996 Genes Dev. 10: 2411–2422

Download references

Acknowledgements

We thank Mike Lasarev for help with the statistical analysis used to plot the cell survival data. This work was supported by NIH grants CA56383 and CA76528 (MS Turker), NS34746 (TK Pandita), and GM49334 (MJ Thayer).

Author information

Authors and Affiliations

  1. Center for Research on Occupational and Environmental Toxicology, Oregon Health Sciences University, Portland, 97201, Oregon, OR, USA

    Blythe M Gage, Daniel Alroy, Chi Y Shin, Olga N Ponomareva & Mitchell S Turker

  2. Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, 10032, NY, USA

    Sonu Dhar, Girdhar G Sharma & Tej K Pandita

  3. Vollum Institute, Oregon Health Sciences University, Portland, 97201, Oregon, OR, USA

    Mathew J Thayer

  4. Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland, 97201, Oregon, OR, USA

    Mathew J Thayer & Mitchell S Turker

Authors
  1. Blythe M Gage
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel Alroy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chi Y Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Olga N Ponomareva
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sonu Dhar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Girdhar G Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Tej K Pandita
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mathew J Thayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mitchell S Turker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mitchell S Turker.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gage, B., Alroy, D., Shin, C. et al. Spontaneously immortalized cell lines obtained from adult Atm null mice retain sensitivity to ionizing radiation and exhibit a mutational pattern suggestive of oxidative stress. Oncogene 20, 4291–4297 (2001). https://doi.org/10.1038/sj.onc.1204509

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204509

Keywords

This article is cited by

Search

Advanced search

Quick links