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

研究成果: ジャーナルへの寄稿学術誌査読

3 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)453-466
ページ数14
ジャーナルJournal of radiation research
54
3
DOI
出版ステータス出版済み - 5月 2013

!!!All Science Journal Classification (ASJC) codes

  • 放射線
  • 放射線学、核医学およびイメージング
  • 健康、毒物学および変異誘発

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