Abstract
γ-irradiated mice develop thymic lymphomas but the incidence varies among different strains. BALB/c(C) mice are highly susceptible to lymphomas whereas MSM(M) mice are resistant. Such difference can be ascribed to genetic polymorphisms but mechanism of the susceptibility remains to be addressed. We previously assigned a lymphoma-susceptibility locus near D5Mit7 locus on mouse chromosome 5. Here we show mapping of this locus using BALB/c congenic mouse lines, line-S3 (substituting a 77.5-104.5 Mb region for MSM) and line-S4 (79.8-116.1 Mb region). Line-S3 showed no difference in lymphoma incidence between congenic mice of C/M and M/M genotypes whereas line-S4 showed a significant difference. The result localized the candidate locus within a 12 Mb region between 104.5 Mb and 116.1 Mb. To further localize the region, we produced other congenic lines (98.1-112.3 Mb and 98.1-104.6 Mb) and subjected to carcinogenesis experiment. In addition, we compared atrophic thymus at 40 and 80 days after irradiation between susceptible and resistant strains, which was predicted to harbor pre-lymphoma cells. Characteristics of thymocytes in those thymuses were clonal proliferation, retention of high ROS, and increase in the percent of G1-phase large-sized cells. Thymocytes in susceptible strain at 80 days, but not 40 days, after irradiation tended to increase in the percent of cells showing the phenotypes more than in resistant strain. We implicate this increase to lymphoma-susceptibility and the clonally proliferating large thymocytes may meet the requirements for pre-lymphoma cells.
