Atm haploinsufficiency does not affect ionizing radiation mutagenesis in solid mouse tissues

Lanelle Connolly, Michael Lasarev, Robert Jordan, Jeffrey L. Schwartz, Mitchell S. Turker

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Ataxia telangiectasia (AT) is a hereditary disease with autosomal recessive inheritance of ATM (ataxia telangiectasia mutation) alleles. AT is associated with severe sensitivity to ionizing radiation and a strong predisposition to develop cancer. A modest increase in cancer, particularly for the breast, has been shown for ATM carriers (i.e. heterozygotes), and a modest increase in radiation sensitivity has also been shown for those patients and their cells. However, the extent of these effects is unclear. Based on the well-established relationship between cancer and mutation, we used a mouse model for Atm haploinsufficiency to ask whether partial loss of Atm function could lead to an increased mutagenic response for solid tissues of mice exposed to radiation. The autosomal mouse Aprt gene was used as the mutational target and kidney and ear as the target tissues in B6D2F1 hybrids. Although induction of autosomal mutations was readily demonstrated in both tissues, a comparison of these data with those from an identical study performed with B6D2F1 mice that were wild-type for Atm (Cancer Res. 62, 1518-1523, 2002) revealed that Atm haploinsufficiency did not alter the radiation mutagenic response for the cells of either tissue. Moreover, no effect of Atm haploinsufficiency on reduced cellular viability due to radiation exposure was observed. The results demonstrate that Atm haploinsufficiency does not alter the radiation mutagenic response or decrease viability for normally quiescent cells in solid tissues of the mouse.

Original languageEnglish (US)
Pages (from-to)39-46
Number of pages8
JournalRadiation research
Volume166
Issue number1 I
DOIs
StatePublished - Jul 1 2006

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

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