@misc{oai:repo.qst.go.jp:00070191,
 author = {Kakinuma, Shizuko and Takimoto, Misaki and Hirano, Shinobu and Nakata, Akifumi and Kodama, Youtarou and Amasaki, Yoshiko and Shang, Yi and Yoshida, Mitsuaki and Nishimura, Mayumi and Shimada, Yoshiya and 柿沼 志津子 and 滝本 美咲 and 坂入 しのぶ and 中田 章史 and 小玉 陽太郎 and 甘崎 佳子 and 尚 奕 and 吉田 光明 and 西村 まゆみ and 島田 義也},
 month = {Jun},
 note = {Background: The carcinogenic effects of ionizing radiation vary markedly with age and genetic background of exposed individuals, as revealed by epidemiological studies such as the survivors of atomic bomb exposure, Chernobyl accidents and medically irradiated patients. We studied effects of age at exposure on radiation carcinogenesis using mouse model for T-cell lymphomas in mismatch repair (MMR)-deficient mice.  Homozygous germline mutations of MMR genes in humans are manifested by an early onset of childhood T- or B-cell leukemias. 
Materials and methods: Mlh1-deficient mice were irradiated with 2Gy of X-rays at late fetal (17 dpc), 2-weeks and 10-weeks of age, and underwent autopsy at the time of spontaneous death.  Collected T-cell lymphomas were examined for the expression and mutation status of Ikaros, which is a potent tumor suppressor for this tumor type in human and mouse.
Results: Mlh1-deficient mice develop T-cell lymphomas spontaneously at the incidence of 71%.  Ionizing radiation exposure further accelerated lymphoma development; 2-week-old mice were more susceptible to radiation than 10-week-old mice.  Radiation-induced lymphoma was characterized by high rate of invasion into other tissues.  Unexpectedly, the 17-dpc mice were resistant.  When lymphomas were molecularly analyzed, the frame shift mutations at mononucleotide repeat sequences in Ikaros gene were frequently observed, which resulted in loss of the protein. The point mutations in either DNA binding domain or dimerization domain was found in 2-week-old (15%) and 10-week-old (46%) irradiated groups.
Conclusion: These results suggest that the age at exposure to ionizing radiation affects not only tumor incidence but also the mechanism of lymphomagenesis., 21st Meeting of the European Association for Cancer Research},
 title = {Age dependence of T-cell lymphoma induction by radiation exposure in Mlh1-deficient mice},
 year = {2010}
}