Xrcc2 modulates spontaneous and radiation-induced tumorigenesis in Apcmin/+ mice.
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.
Haines
Jackie W
JW
Health Protection Agency, Centre for Radiation, Chemical and Environmental Hazards, Chilton, Oxfordshire OX11 0RQ, United Kingdom. jackie.haines@hpa.org.uk
Coster
Margaret R
MR
Adam
Julie
J
Cheeseman
Michael
M
Ainsbury
Elizabeth A
EA
Thacker
John
J
Bouffler
Simon D
SD
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
D004268:DNA-Binding Proteins; C491866:Xrcc2 protein, mouse