Susceptibility Loci and Chromosomal Abnormalities in Radiation Induced Hematopoietic Neoplasms in Mice

Radiation induced lymphoma/Radiation induced myeloid-granulocytic leukemia/Susceptibility genes/Chromosomal abnormalities. Genetics of susceptibility to radiation-induced hema topoietic neoplasms and somatic chromosomal aberrations were analyzed in 305 backcross (CcS-17xCcS-2)xCcS-2 mice of two CcS/Dem recombinant congenic strains. Irradiated CcS-2 mice were previously shown to exhibit high frequency of myeloid neoplasms whereas irradiated CcS-17 mice were susceptib le to T-cell lymphomas. Mice were exposed to four whole-body irradiation doses of 1.7 Gy at one week intervals, which resulted in 139 hematopoietic neoplasms. The hematopoietic neoplasms were classified according to the Bethesda proposals for classification of lymphoid and nonlymphoid hematopoietic neoplasms in mice. Genotyping of mice with 24 microsatellite markers and subsequent statistical analysis indicated linkage of the radiation induced T-lymphomas to two loci on chromosome 10 (D10Mit134) and chromosome 12 (D12Mit52). T-lymphoma susceptibility appeared to be linked to D10Mit134 in a sex dependent way. In contrast, the myeloidgranulocytic leukemias susceptibility is linked to combined effects of chromosome 5 (D5Mit179) and 16 (D16Mit34). Cytogenetic analysis was performed according to the standard G-bands procedure and confirmed using FISH method. We found non-random numerical and structural chromosomal changes in lymphoid neoplasms. Cytogenetic analysis indicated chromosomal aberrations presumably associated with lymp homagenesis, no specific cancer-related rearrangements were observed.