Heterozygosity for a mutation in Brca1 or Atm does not increase susceptibility to ENU-induced mammary tumors in Apc(Min)/+ mice

The proteins encoded by BRCA1 and ATM may be important in DNA repair and ma intenance of genomic integrity. Women heterozygous for a mutation in BRCA1 have an increased incidence of breast cancer, Some evidence also suggests t hat female carriers of ATM mutations may be susceptible to breast cancer. H owever, mice carrying one mutant allele of Brca1 or Atm are not highly susc eptible to breast cancer. We proposed that heterozygosity for a mutant alle le of Brca1 or Atm may confer a decreased ability to repair DNA damage. Suc h a defect might lead to a heightened sensitivity to tumor development in s usceptible animal models. Therefore, mice predispose to mammary tumor devel opment might show an increased susceptibility if they also carry an Atm or Brca1 mutation. C57BL/6J (B6) Min/+ mice are predisposed to mammary and int estinal tumors and exposure to the point mutagen ethylnitrosourea (ENU) mar kedly increases mammary tumor multiplicity and incidence. To test our hypot hesis, B6.Min/+ male mice were crossed with 129S6/SvEvTac females heterozyg ous for a mutant allele of either Brca1 or Atm, Female progeny from each cr oss were treated with ENU and followed for tumor development. Only Min/+ Fl females developed mammary tumors and heterozygosity for a mutant Brca1 or Atm allele had no effect on mammary or intestinal tumor incidence and multi plicity. These results suggest that heterozygosity for a mutation in Brca1 or Atm does not affect Min-induced tumorigenesis in mice under these condit ions. Additionally, exposure to a somatic point mutagen does not increase t umor development in mice carrying Brca1 or Atm mutations.