Myeloid, B and T lymphoid and mixed lineage thymic lymphomas in the irradiated mouse

Abstract

Thymic lymphoma is a very common spontaneous and/or induced malignancy in both inbred mice and in transgenic mouse models of human cancer. Although a thymic lymphoma is defined as thymus-dependent T-cell malignancy, diagnostic criteria vary between studies and considerable heterogeneity has been reported. To define and classify the thymic lymphomas that arose in our study of X-irradiated (CBA/HxC57BL/6)F1, F1 backcross and F1 intercross mice, 66 thymic lymphomas were immunogenotyped for immunoglobulin heavy chain (IgH) and T-cell receptor beta (TCRbeta) gene rearrangements, and/or analysed for expression of lineage-specific markers and allelic loss on chromosome 4. The data indicate that 33% of the thymic lymphomas are very similar to mouse radiation-induced acute myeloid (AML) and mixed lineage (IgH(R), TCRbeta(G)) pre-B lympho-myeloid (L-MLs) leukaemias, 33% are mixed lineage (IgH(R), TCRbeta(R)) B/T lymphoid and <33% can be described as single lineage (IgH(G), TCRbeta(R)) T-cell malignancies. As the myeloid and L-ML leukaemias are not thymus-dependent this suggests that a malignant myeloid or pre-B lympho-myeloid cell can colonize the spleen to give an AML or L-ML leukaemia, or can colonize the thymus where TCRbeta gene rearrangement(s) may be induced to give the mixed lineage thymic lymphomas. Thus, assuming the single lineage T-cell thymic lymphomas fulfil the criteria of a thymus-dependent T-cell malignancy, thymic lymphomas are comprised of at least three distinct malignancies.

Fractionated Low-Dose Radiation Exposure Leads to Accumulation of DNA Damage and Profound Alterations in DNA and Histone Methylation in the Murine Thymus

“…In the current study, an even more considerable loss of methylation was observed in the thymus tissue. The spleen and thymus are important parts of hematopoietic and lymphatic tissue and are profoundly affected in lymphomas and leukemias (31)(32)(33).…”

“…The murine model is widely used, well characterized, and generally accepted for studies of radiation-induced changes in hematopoietic and lymphatic tissue (31)(32)(33). Handling and care of animals was in strict accordance with the recommendations of the Canadian Council for Animal Care and Use.…”

“…Due to the paucity of data in this area, in the present study, we investigated the effect of low-dose radiation exposure on accumulation of DNA lesions and alterations of DNA and histone methylation in thymus tissue using an in vivo murine model (31)(32)(33). Radiation exposure induces leukemia and lymphoma in rodents; therefore, the rodent model has become a valuable system for delineating molecular mechanisms of radiationinduced leukemia and lymphoma predisposition (31)(32)(33).…”

“…Radiation exposure induces leukemia and lymphoma in rodents; therefore, the rodent model has become a valuable system for delineating molecular mechanisms of radiationinduced leukemia and lymphoma predisposition (31)(32)(33).…”

Radiation‐induced bystander effects in vivo are epigenetically regulated in a tissue‐specific manner

“…Spleen and skin tissue located above spleen were sampled upon sacrifice and processed for further molecular studies. Both spleen and skin are radiation targets organs and are linked to radiation carcinogenesis [Shore, 1990;Boulton et al, 2002].…”