@misc{oai:repo.qst.go.jp:00063947,
 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 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 島田 義也},
 month = {Dec},
 note = {TThe 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 models for T-cell lymphomas in B6C3F1 and Mlh1-defficient mice as a wild type and a mismatch repair (MMR) deficient-type model, respectively. Homozygous germline mutations of MMR genes in humans are manifested by an early onset of childhood T- or B-cell leukemias, while Mlh1-deficient mice develop T-cell lymphomas spontaneously. 
We previously reported that X-ray induced lymphomas had unique locus with high frequency of loss of heterozygosity (LOH) in the centromeric region of chromosome 11. This unique LOH was rarely observed in N-ethyl-N-nitrosourea (ENU)-induced or spontaneously developing lymphomas. This LOH could be a specific molecular change associated with radiation exposure (radiation signature). Further study suggested, Ikaros, which was mapped in the LOH region of chromosome 11, was frequently mutated in the radiation-induced lymphomas in mice. Ikaros is a transcription factor that plays a key role in lineage commitment and differentiation of lymphoid cells and is also known as a tumor suppressor that is frequently altered in both human and mouse lymphomas.  Our molecular analysis revealed that Ikaros was inactivated either by transcriptional silencing, aberrant splicing or point mutations.
In order to further elucidate the age dependence of X-ray-induced lymphomagenesis, B6C3F1 mice were irradiated at the age of 1, 4, 8, 12, 24 weeks after birth. When mice were irradiated at the age 1 and 4-weeks were susceptible to radiation lymphomagenesis. However, chromosomal abnormalities and LOH frequency were different between these two groups. When Mlh1-deficient mice were irradiated at late fetal (17 dpc), 2-week- and 10-week-old, 2-week-old mice were more susceptible to radiation than 10-week-old mice, but the 17-dpc mice were unexpectedly resistant. When lymphoma tissue were further analyzed, the frequent frame shift mutations at mononucleotide repeat sequences in Ikaros were observed and which had been resulted in loss of the protein. These results suggest that the age at exposure to radiation changes not only tumor incidence but also the mechanism of lymphomagenesis., KIDS workshop 2009 in NIRS - IAEA NIRS Joint Workshop & NIRS Symposium on Radiation Protection for Children},
 title = {Age dependence of T-cell lymphoma induction by radiation exposure in B6C3F1 and Mlh1-deficient mice},
 year = {2009}
}