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Age dependence of T-cell lymphoma induction by radiation exposure in B6C3F1 and Mlh1-deficient mice
https://repo.qst.go.jp/records/63947
https://repo.qst.go.jp/records/63947b7e1691c-ee3a-48d3-93b6-e2c867b1961e
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2010-07-09 | |||||
| タイトル | ||||||
| タイトル | Age dependence of T-cell lymphoma induction by radiation exposure in B6C3F1 and Mlh1-deficient mice | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
| 資源タイプ | conference object | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Kakinuma, Shizuko
× Kakinuma, Shizuko× Takimoto, Misaki× Hirano, Shinobu× Nakata, Akifumi× Kodama, Youtarou× Amasaki, Yoshiko× Shang, Yi× Yoshida, Mitsuaki× Shimada, Yoshiya× 柿沼 志津子× 滝本 美咲× 坂入 しのぶ× 中田 章史× 小玉 陽太郎× 甘崎 佳子× 尚 奕× 吉田 光明× 島田 義也 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 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. |
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| 会議概要（会議名, 開催地, 会期, 主催者等） | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | KIDS workshop 2009 in NIRS - IAEA NIRS Joint Workshop & NIRS Symposium on Radiation Protection for Children | |||||
| 発表年月日 | ||||||
| 日付 | 2009-12-16 | |||||
| 日付タイプ | Issued | |||||
