Xrcc2 Modulates Spontaneous and Radiation-Induced Tumorigenesis in Apc > min/+ Mice

Jackie W. Haines*, Margaret R. Coster, Julie Adam, Michael Cheeseman, Elizabeth A. Ainsbury, John Thacker, Simon D. Bouffler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

XRCC2 has an important role in repair of DNA damage by homologous recombination. Adult Apc(min/+) (min, multiple intestinal neoplasia) mice, wild-type or heterozygous for Xrcc2 deficiency, were sham-irradiated or 2-Gy X-irradiated. Spontaneous mammary and intestinal tumor incidences are lower in Apc(min/+) Xrcc2(+/-) mice than in Apc(min/+) Xrcc2(+/+) mice (mammary tumors: 14% and 38%, respectively, chi(2) P = 0.03; intestinal adenomas in mice reaching full life span: 108.6 and 130.1, respectively, t-test P = 0.005). Following irradiation, the increase in mammary tumors was greatest in female mice heterozygous for Xrcc2 (7.25 +/- 0.50-fold in Apc(min/+) Xrcc2(+/-) mice compared with 2.57 +/- 0.35-fold in Apc(min/+) Xrcc2(+/+) mice; t-test P <0.001). The increase in intestinal tumor multiplicity following irradiation was significantly greater in Apc(min/+) Xrcc2(+/-) mice (Apc(min/+) Xrcc2(+/-), 4.14 +/- 0.05-fold, versus Apc(min/+) Xrcc2(+/+), 3.30 +/- 0.05-fold; t-test P <0.001). Loss of heterozygosity of all chromosome 18 markers was greater in intestinal tumors from Apc(min/+) Xrcc2(+/-) mice than in tumors from Apc(min/+) Xrcc2(+/+) mice. These findings indicate that Xrcc2 haploinsufficiency reduces spontaneous tumor incidence on an Apc(min/+) background but increases the tumorigenic response to radiation. Mol Cancer Res; 8(9); 1227-33. (C)2010 AACR.

Original languageEnglish
Pages (from-to)1227-1233
Number of pages7
JournalMolecular Cancer Research
Volume8
Issue number9
DOIs
Publication statusPublished - Sep 2010

Keywords

  • PREDISPOSES
  • BREAST-CANCER SUSCEPTIBILITY
  • ADENOMA MULTIPLICITY
  • TUMOR-FORMATION
  • DNA-DAMAGE
  • MUTATION
  • REPAIR GENES
  • MOUSE
  • BRCA1
  • APC(MIN)

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