Nature of nontargeted radiation effects observed during fractionated irradiation-induced thymic lymphomagenesis in mice

Hideo Tsuji, Hiroko Ishii-Ohba, Tadahiro Shiomi, Naoko Shiomi, Takanori Katsube, Masahiko Mori, Mitsuru Nenoi, Mizuki Ohno, Daisuke Yoshimura, Sugako Oka, Yusaku Nakabeppu, Kouichi Tatsumi, Masahiro Muto, Toshihiko Sado

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Changes in the thymic microenvironment lead to radiation-induced thymic lymphomagenesis, but the phenomena are not fully understood. Here we show that radiation-induced chromosomal instability and bystander effects occur in thymocytes and are involved in lymphomagenesis in C57BL/6 mice that have been irradiated four times with 1.8-Gy γ-rays. Reactive oxygen species (ROS) were generated in descendants of irradiated thymocytes during recovery from radiation-induced thymic atrophy. Concomitantly, descendants of irradiated thymocytes manifested DNA lesions as revealed by γ-H2AX foci, chromosomal instability, aneuploidy with trisomy 15 and bystander effects on chromosomal aberration induction in co-cultured ROS-sensitive mutant cells, suggesting that the delayed generation of ROS is a primary cause of these phenomena. Abolishing the bystander effect of post-irradiation thymocytes by superoxide dismutase and catalase supports ROS involvement. Chromosomal instability in thymocytes resulted in the generation of abnormal cell clones bearing trisomy 15 and aberrant karyotypes in the thymus. The emergence of thymic lymphomas from the thymocyte population containing abnormal cell clones indicated that clones with trisomy 15 and altered karyotypes were prelymphoma cells with the potential to develop into thymic lymphomas. The oncogene Notch1 was rearranged after the prelymphoma cells were established. Thus, delayed nontargeted radiation effects drive thymic lymphomagenesis through the induction of characteristic changes in intrathymic immature T cells and the generation of prelymphoma cells.

Original languageEnglish
Pages (from-to)453-466
Number of pages14
JournalJournal of radiation research
Volume54
Issue number3
DOIs
Publication statusPublished - May 1 2013

Fingerprint

Radiation Effects
radiation effects
Thymocytes
mice
clone cells
Bystander Effect
Chromosomal Instability
irradiation
Reactive Oxygen Species
Trisomy
oxygen
cells
induction
radiation
Clone Cells
oncogenes
Radiation
atrophy
Karyotype
catalase

All Science Journal Classification (ASJC) codes

  • Radiation
  • Radiology Nuclear Medicine and imaging
  • Health, Toxicology and Mutagenesis

Cite this

Nature of nontargeted radiation effects observed during fractionated irradiation-induced thymic lymphomagenesis in mice. / Tsuji, Hideo; Ishii-Ohba, Hiroko; Shiomi, Tadahiro; Shiomi, Naoko; Katsube, Takanori; Mori, Masahiko; Nenoi, Mitsuru; Ohno, Mizuki; Yoshimura, Daisuke; Oka, Sugako; Nakabeppu, Yusaku; Tatsumi, Kouichi; Muto, Masahiro; Sado, Toshihiko.

In: Journal of radiation research, Vol. 54, No. 3, 01.05.2013, p. 453-466.

Research output: Contribution to journalArticle

Tsuji, H, Ishii-Ohba, H, Shiomi, T, Shiomi, N, Katsube, T, Mori, M, Nenoi, M, Ohno, M, Yoshimura, D, Oka, S, Nakabeppu, Y, Tatsumi, K, Muto, M & Sado, T 2013, 'Nature of nontargeted radiation effects observed during fractionated irradiation-induced thymic lymphomagenesis in mice', Journal of radiation research, vol. 54, no. 3, pp. 453-466. https://doi.org/10.1093/jrr/rrs128
Tsuji, Hideo ; Ishii-Ohba, Hiroko ; Shiomi, Tadahiro ; Shiomi, Naoko ; Katsube, Takanori ; Mori, Masahiko ; Nenoi, Mitsuru ; Ohno, Mizuki ; Yoshimura, Daisuke ; Oka, Sugako ; Nakabeppu, Yusaku ; Tatsumi, Kouichi ; Muto, Masahiro ; Sado, Toshihiko. / Nature of nontargeted radiation effects observed during fractionated irradiation-induced thymic lymphomagenesis in mice. In: Journal of radiation research. 2013 ; Vol. 54, No. 3. pp. 453-466.
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AU - Shiomi, Naoko

AU - Katsube, Takanori

AU - Mori, Masahiko

AU - Nenoi, Mitsuru

AU - Ohno, Mizuki

AU - Yoshimura, Daisuke

AU - Oka, Sugako

AU - Nakabeppu, Yusaku

AU - Tatsumi, Kouichi

AU - Muto, Masahiro

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