THYMUS CELL POPULATION STUDIES DURING RADIATION LEUKEMOGENESIS

The cell population structure and proliferative characteristics in the thymus of young C₅₇BL mice during radiation lymphomogenesis are examined.

Initially, there was cellular depopulation followed by regeneration to a normal cell level by about 11 weeks. In a large proportion of animals, however, if the observation period is long enough, at least one surviving cell mutates and the animals develop lymphoma. Tritiated thymidine labeling indexes increased during this period, particularly in the medium and small lymphoid cell compartments, to twice normal levels by 13 weeks, at the time of thymic lymphoma, and to four-fold normal values by 25 weeks, at the time of disseminated lymphoma. The proliferative fraction increased greatly during this interval. This may have been due to a greater proportion of cells proliferating in the medium and small lymphocyte compartments and bringing into proliferation nondividing cells which still have proliferative potential. However, the proliferation rate is decreased as indicated by an increase in the duration of the median lymphoid cell cycle time in successive generations. On the basis of the proportion of large lymphoid cells, and increased labeling among the small and medium lymphoid cells, it is probable that factors contributing to lymphoma development involve a progressive breakdown of internal and external cellular control mechanisms, loss of the capacity to differentiate among primitive cells and possibly transformation of basically nonproliferating functional end cells to more primitive proliferative forms.

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