- 作者：Takashi Yamamoto ; Shin-ichi Morita ; Rieka Go ; Miki Obata ; Yoshinori Katsuragi ; Yukari Fujita ; Yoshitaka Maeda ; Minesuke Yokoyama ; Yutaka Aoyagi ; Hitoshi Ichikawa ; Yukio Mishima ; Ryo Kominami
- 刊名：International Journal of Radiation Oncology*Biology*Physics
- 出版年：2010
- 出版时间：1 May 2010
- 年：2010
- 卷：77
- 期：1
- 页码：235-243
- 全文大小：950 K
Purpose
To characterize, in the setting of γ-ray–induced atrophic thymus, probable prelymphoma cells showing clonal growth and changes in signaling, including DNA damage checkpoint.Methods and Materials
A total of 111 and 45 mouse atrophic thymuses at 40 and 80 days, respectively, after γ-irradiation were analyzed with polymerase chain reaction for D-J rearrangements at the TCRβ locus, flow cytometry for cell cycle, and Western blotting for the activation of DNA damage checkpoints.
Results
Limited D-J rearrangement patterns distinct from normal thymus were detected at high frequencies (43 of 111 for 40-day thymus and 21 of 45 for 80-day thymus). Those clonally expanded thymocytes mostly consisted of CD4+CD8+ double-positive cells, indicating the retention of lineage capability. They exhibited pausing at a late G1 phase of cell cycle progression but did not show the activation of DNA damage checkpoints such as γH2AX, Chk1/2, or p53. Of interest is that 17 of the 52 thymuses showing normal D-J rearrangement patterns at 40 days after irradiation showed allelic loss at the Bcl11b tumor suppressor locus, also indicating clonal expansion.
Conclusion
The thymocytes of clonal growth detected resemble human chronic myeloid leukemia in possessing self-renewal and lineage capability, and therefore they can be a candidate of the lymphoma-initiating cells.