Journal Article

Heterozygosity for a mutation in <i>Brca1</i> or <i>Atm</i> does not increase susceptibility to ENU-induced mammary tumors in <i>Apc</i><sup>Min</sup>/+ mice

Melissa E. Karabinis, Denise Larson, Carrolee Barlow, Anthony Wynshaw-Boris and Amy Rapaich Moser

in Carcinogenesis

Volume 22, issue 2, pages 343-346
Published in print February 2001 | ISSN: 0143-3334
Published online February 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.2.343
Heterozygosity for a mutation in Brca1 or Atm does not increase susceptibility to ENU-induced mammary tumors in ApcMin/+ mice

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The proteins encoded by BRCA1 and ATM may be important in DNA repair and maintenance of genomic integrity. Women heterozygous for a mutation in BRCA1 have an increased incidence of breast cancer. Some evidence also suggests that female carriers of ATM mutations may be susceptible to breast cancer. However, mice carrying one mutant allele of Brca1 or Atm are not highly susceptible to breast cancer. We proposed that heterozygosity for a mutant allele of Brca1 or Atm may confer a decreased ability to repair DNA damage. Such a defect might lead to a heightened sensitivity to tumor development in susceptible animal models. Therefore, mice predispose to mammary tumor development might show an increased susceptibility if they also carry an Atm or Brca1 mutation. C57BL/6J (B6) Min/+ mice are predisposed to mammary and intestinal tumors and exposure to the point mutagen ethylnitrosourea (ENU) markedly increases mammary tumor multiplicity and incidence. To test our hypothesis, B6.Min/+ male mice were crossed with 129S6/SvEvTac females heterozygous for a mutant allele of either Brca1 or Atm. Female progeny from each cross were treated with ENU and followed for tumor development. Only Min/+ F1 females developed mammary tumors and heterozygosity for a mutant Brca1 or Atm allele had no effect on mammary or intestinal tumor incidence and multiplicity. These results suggest that heterozygosity for a mutation in Brca1 or Atm does not affect Min-induced tumorigenesis in mice under these conditions. Additionally, exposure to a somatic point mutagen does not increase tumor development in mice carrying Brca1 or Atm mutations.

Keywords: AT, ataxia telangiectasia; ENU, ethylnitrosourea.

Journal Article.  2816 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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