Humblet C, Deman J, Franzen R, Greimers R, Boniver J, Defresne M P
Laboratory of Pathological Anatomy, University of Liège, Belgium.
Stem Cells. 1995 May;13 Suppl 1:129-35.
Radio-induced thymic lymphomagenesis is associated with alterations in the balance between thymocyte subsets and cytokinetic perturbations. The objectives of this work were to investigate whether these alterations are associated with alterations in the basic levels of thymocyte apoptosis. For this purpose, we tested DNA fragmentation by gel electrophoresis, analyzed DNA content by propidium iodide staining of ethanol fixed cells and looked for DNA strand breaks on tissue sections by in situ end labeling. We described an increase of the levels of apoptosis in cultured thymocytes during the preleukemic period, while the basic levels of apoptosis observed in situ are similar in normal and in preleukemic thymuses. We propose that after leukemogenic irradiations, there is an increase of cells wherein the cell suicide program is activated but that environmental thymic factors rescue them from apoptosis. Preleukemic cells could belong to this abnormally surviving population of cells "programmed to die," wherein additional genomic abnormalities would lead to fully neoplastic transformation.
辐射诱导的胸腺淋巴瘤发生与胸腺细胞亚群平衡的改变以及细胞动力学紊乱有关。本研究的目的是调查这些改变是否与胸腺细胞凋亡的基础水平改变有关。为此,我们通过凝胶电泳检测DNA片段化,用碘化丙啶对乙醇固定的细胞进行染色以分析DNA含量,并通过原位末端标记在组织切片上寻找DNA链断裂。我们描述了在白血病前期培养的胸腺细胞中凋亡水平的增加,而原位观察到的正常和白血病前期胸腺的凋亡基础水平相似。我们提出,在致白血病辐射后,激活细胞自杀程序的细胞数量增加,但胸腺环境因素使它们免于凋亡。白血病前期细胞可能属于这种“程序性死亡”的异常存活细胞群体,其中额外的基因组异常将导致完全的肿瘤转化。