title: Xrcc2 modulates spontaneous and radiation-induced tumorigenesis in Apcmin/+ mice.
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, χ(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.
authors.affiliation: Health Protection Agency, Centre for Radiation, Chemical and Environmental Hazards, Chilton, Oxfordshire OX11 0RQ, United Kingdom. jackie.haines@hpa.org.uk
authors.forename: Jackie W
authors.initials: JW
authors.lastname: Haines
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Coster
authors.forename: Julie
authors.initials: J
authors.lastname: Adam
authors.forename: Michael
authors.initials: M
authors.lastname: Cheeseman
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Ainsbury
authors.forename: John
authors.initials: J
authors.lastname: Thacker
authors.forename: Simon D
authors.initials: SD
authors.lastname: Bouffler
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000378:metabolism*; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D007414:Intestinal Neoplasms / Q000235:genetics / Q000473:pathology*; D019656:Loss of Heterozygosity / Q000235:genetics; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D051379:Mice; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D014965:X-Rays
chemical_list: D004268:DNA-Binding Proteins; C491866:Xrcc2 protein, mouse