Ikaros is a potent tumor suppressor gene in both human and murine leukemogenesis. We previously showed Ikaros alteration type is differed between X-ray-induced murine thymic lymphoma (TL) and N-ethyl-N-nitrosourea (ENU) -induced TL. Thus, X-ray-induced TL was characterized by altered splicing, null expression and point mutations, which were accompanied by by loss of heterozygosity (LOH). ENU-induced TL harbored only point mutation without LOH. We showed that combined treatment of X-rays (0.8-1.0 Gy x 4 times) and ENU (100, 200ppm) synergistically increased TL incidence. The aim of the curresnt study is to elucidate the underlying mechanism in the lymphomagenesis induced by combined treatment of X-rays and ENU. In this study, we analyzed the mutation status of Ikaros in the TLs induced by combined (X-rays following ENU) treatment. B6C3F1 mice (4-week-old female) were irradiated by X-rays (0.2 - 1.0 Gy a week x 4 times) and then treated by EMU (50 - 200 ppm in drinking water) from 8-week-old. The analyses of LOH on chromosome 11, expression by RT-PCR and western blotting, and mutation by sequence were performed. Ikaros splicing and null expression was observed in X-ray-induced TL was 10 and12%, ENU-induced TL was both 0%, combined-induced TL was 6 and 0%. Point mutation and LOH status were 26%(LOH:73%) in X-ray-induced TL 26%(LOH:0%) in ENU-induced TL. In combined-induced TL, that was increased to 40% (LOH: 20%), it is ENU type. Thus, X-rays plays a promoter for ENU-induced leukemogenesis in the TL induced by X-rays following ENU.第48回日本放射線影響学会／第1回アジア放射線研究会
