Analysis of early initiating event(s) in radiation-induced thymic lymphomagenesis

Since the T cell receptor rearrangement is a sequential process and unique to the progeny of each clone, we investigated the early initiating events in radiation-induced thymic lymphomagenesis by comparing the oncogenic alterations with the pattern of gamma T cell receptor (TCR) rearrangements. We reported previously that after leukemogenic irradiation, preneoplastic cells developed, albeit infrequently, from thymic leukemia antigen-2+ (TL-2+) thymocytes. Limited numbers of TL-2+ cells from individual irradiated B10.Thy 1.1 mice were injected into B10.Thy 1.2 mice intrathymically, and the common genetic changes among the donor-type T cell lymphomas were investigated with regard to p53 gene and chromosome aberrations. The results indicated that some mutations in the p53 gene had taken place in these lymphomas, but there was no common mutation among the donor-type lymphomas from individual irradiated mice, suggesting that these mutations were late-occurring events in the process of oncogenesis. On the other hand, there were common chromosome aberrations or translocations such as trisomy 15, t(7F;10C), t(1A;13D) or t(6A;XB) among the donor-type lymphomas derived from half of the individual irradiated mice. This indicated that the aberrations/translocations, which occurred in single progenitor cells at the early T cell differentiation either just before or after gamma T cell receptor rearrangements, might be important candidates for initiating events. In the donor-type lymphomas from the other half of the individual irradiated mice, microgenetic changes were suggested to be initial events and also might take place in single progenitor cells just before or right after gamma TCR rearrangements.