Clonally Expanding Thymocytes Having Lineage Capability in Gamma-Ray-Induced Mouse Atrophic Thymus

Journal Article · Sat May 01 00:00:00 EDT 2010 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2009.11.005· OSTI ID:21372265

Yamamoto, Takashi; Morita, Shin-ichi ^[1]; Go, Rieka; Obata, Miki; Katsuragi, Yoshinori; Fujita, Yukari ^[1]; Maeda, Yoshitaka; Yokoyama, Minesuke ^[2]; Aoyagi, Yutaka ^[3]; Ichikawa, Hitoshi ^[4]; Mishima, Yukio ^[1]; Kominami, Ryo ^[1]

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1. Department of Molecular Genetics, Niigata University Graduate School of Medical and Dental Sciences, Niigata (Japan)
2. Center for Bioresource-Based Researches, Brain Research Institute, Niigata (Japan)
3. Department of 3rd Internal Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata (Japan)
4. Genetics Division, National Cancer Center Research Institute, Tokyo (Japan)

Purpose: To characterize, in the setting of gamma-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 gamma-irradiation were analyzed with polymerase chain reaction for D-J rearrangements at the TCRbeta 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{sup +}CD8{sup +} 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 gammaH2AX, 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.

• OSTI ID: 21372265
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 77, Issue 1; Other Information: DOI: 10.1016/j.ijrobp.2009.11.005; PII: S0360-3016(09)03454-3; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS
BIOLOGICAL RADIATION EFFECTS
CELL CYCLE
DNA DAMAGES
GAMMA RADIATION
LYMPHOMAS
MYELOID LEUKEMIA
POLYMERASE CHAIN REACTION
THYMOCYTES
THYMUS
ANIMAL CELLS
BIOLOGICAL EFFECTS
BODY
DISEASES
ELECTROMAGNETIC RADIATION
GENE AMPLIFICATION
IMMUNE SYSTEM DISEASES
IONIZING RADIATIONS
LEUKEMIA
LYMPHATIC SYSTEM
NEOPLASMS
ORGANS
RADIATION EFFECTS
RADIATIONS
SOMATIC CELLS