TY - JOUR
T1 - Xrcc2 modulates spontaneous and radiation-induced tumorigenesis in Apc min/+ mice
AU - Haines, Jackie W.
AU - Coster, Margaret R.
AU - Adam, Julie
AU - Cheeseman, Michael
AU - Ainsbury, Elizabeth A.
AU - Thacker, John
AU - Bouffler, Simon D.
PY - 2010/9
Y1 - 2010/9
N2 - XRCC2 has an important role in repair of DNA damage by homologous recombination. Adult Apcmin/+ (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 Apcmin/+ Xrcc2+/- mice than in Apcmin/+ Xrcc2+/+ mice (mammary tumors: 14% and 38%, respectively, χ2 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 Apcmin/+ Xrcc2+/- mice compared with 2.57 ± 0.35-fold in Apcmin/+ Xrcc2+/+ mice; t-test P < 0.001). The increase in intestinal tumor multiplicity following irradiation was significantly greater in Apcmin/+ Xrcc2+/- mice (Apcmin/+ Xrcc2+/-, 4.14 ± 0.05-fold, versus Apcmin/+ 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 Apcmin/+ Xrcc2 +/- mice than in tumors from Apcmin/+ Xrcc2+/+ mice. These findings indicate that Xrcc2 haploinsufficiency reduces spontaneous tumor incidence on an Apcmin/+ background but increases the tumorigenic response to radiation.
AB - XRCC2 has an important role in repair of DNA damage by homologous recombination. Adult Apcmin/+ (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 Apcmin/+ Xrcc2+/- mice than in Apcmin/+ Xrcc2+/+ mice (mammary tumors: 14% and 38%, respectively, χ2 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 Apcmin/+ Xrcc2+/- mice compared with 2.57 ± 0.35-fold in Apcmin/+ Xrcc2+/+ mice; t-test P < 0.001). The increase in intestinal tumor multiplicity following irradiation was significantly greater in Apcmin/+ Xrcc2+/- mice (Apcmin/+ Xrcc2+/-, 4.14 ± 0.05-fold, versus Apcmin/+ 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 Apcmin/+ Xrcc2 +/- mice than in tumors from Apcmin/+ Xrcc2+/+ mice. These findings indicate that Xrcc2 haploinsufficiency reduces spontaneous tumor incidence on an Apcmin/+ background but increases the tumorigenic response to radiation.
UR - http://www.scopus.com/inward/record.url?scp=77957114317&partnerID=8YFLogxK
U2 - 10.1158/1541-7786.MCR-10-0089
DO - 10.1158/1541-7786.MCR-10-0089
M3 - Article
C2 - 20671066
AN - SCOPUS:77957114317
SN - 1541-7786
VL - 8
SP - 1227
EP - 1233
JO - Molecular Cancer Research
JF - Molecular Cancer Research
IS - 9
ER -