Apoptosis during the development of radiogenic thymic lymphomas: effects of treatments inhibiting lymphoma development.
BACKGROUND
Whole body fractionated irradiation induces thymic lymphomas in C57BL/Ka mice after a latent period during which preleukemic cells progressively transform into leukemic cells within an abnormal thymic microenvironment. A bone marrow graft or repeated cytokine injections prevent lymphoma development. We think that these treatments restore altered mechanisms controlling apoptosis.


METHODS
Apoptosis was analyzed by flow cytometry in thymocytes from different groups of mice (control, preleukemic, prevented mice).


RESULTS
The apoptotic rates did not change in freshly isolated thymocytes from different experimental groups. However, after culture, the level of apoptosis increased in preleukemic thymuses; and returned to normal value in cultured thymocytes from irradiated mice after lymphoma preventing treatments. Furthermore, thymic microenvironmental factors can control thymocyte apoptosis.


CONCLUSIONS
We propose that after leukemogenic irradiation, there is an increase of cells with an activated suicide program, but that alterations of thymic environmental factors rescue them from apoptosis, allowing their further neoplastic transformation.
Humblet
C
C
Laboratory of Pathological Anatomy and Cytology, University Hospital of Liege, Belgium.
Denis
G
G
Greimers
R
R
Boniver
J
J
Defresne
M P
MP
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000235:genetics; D016026:Bone Marrow Transplantation; D002471:Cell Transformation, Neoplastic; D053938:DNA Fragmentation; D005260:Female; D005434:Flow Cytometry; D016898:Interferon-alpha / Q000627:therapeutic use; D007371:Interferon-gamma / Q000627:therapeutic use; D008223:Lymphoma / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009381:Neoplasms, Radiation-Induced / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D013953:Thymus Neoplasms / Q000503:physiopathology / Q000517:prevention & control*
D000970:Antineoplastic Agents; D016898:Interferon-alpha; D007371:Interferon-gamma