Limiting dilution analysis of T-cell progenitors in the bone marrow of thymic lymphoma-susceptible B10 and -resistant C3H mice after fractionated whole-body X-irradiation.
Earlier studies from this laboratory using Thy 1 congenic B10 strain mice suggested that a depletion of T cell progenitors (pre T cells) in the bone marrow in addition to the destruction of the thymus after fractionated whole body X-irradiation (IR) are the two main critical factors that cause differentiation arrest of initially repopulating intrathymic radio-resistant T cell progenitors, which then lead to the appearance of preneoplastic, prelymphoma cells, and eventually to highly neoplastic thymic lymphomas under the influence of the thymic environment. In order to explore the significance of the depletion (or reduction) of T cell progenitors in the bone marrow during pathogenesis of radiation-induced thymic lymphomas, we compared the pool size of pre T cells in the bone marrow and the spleens as well as the profiles of the regenerating thymocyte populations between thymic lymphoma induction-susceptible B10 and -resistant C3H strain mice following irradiation. The results indicated that irradiation severely depleted the pre T cells in the bone marrow and the spleens of both lymphoma induction-susceptible and -resistant mice. They also showed that in C3H mice the differentiation and maturation of intrathymic T cell progenitors which initially repopulated the depleted thymus seemed to proceed normally in spite of the poor cellularity, while this process was greatly suppressed in B10 mice. These data indicate that a depletion of pre T cells in the bone marrow combined with atrophy of the thymus in the irradiated mice is necessary, but not sufficient for development of thymic lymphoma. Implication of these findings on the possible mechanism of radiation-induced thymic lymphomagenesis is discussed.
Kamisaku
H
H
Division of Biology and Oncology, National Institute of Radiological Sciences, Chiba, Japan.
Aizawa
S
S
Kitagawa
M
M
Ikarashi
Y
Y
Sado
T
T
D000818:Animals; D001853:Bone Marrow / Q000528:radiation effects; D001854:Bone Marrow Cells; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000528:radiation effects*; D007113:Immunity, Innate; D007201:Indicator Dilution Techniques; D008223:Lymphoma / Q000473:pathology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012038:Regeneration; D013601:T-Lymphocytes / Q000166:cytology* / Q000528:radiation effects; D018800:Thy-1 Antigens / Q000032:analysis / Q000528:radiation effects; D013950:Thymus Gland / Q000502:physiology / Q000528:radiation effects; D013953:Thymus Neoplasms / Q000473:pathology*; D014916:Whole-Body Irradiation
D018800:Thy-1 Antigens