Age dependent of Ikaros mutation in mouse thymic lymphoma induced by simultaneous exposure of X-rays and N-ethyl-N-nitrosourea

Abstract

Radiation carcinogenesis in human is considered as a result of the combined effect of radiation and environment factors. In our ordinary life, the simultaneous exposure of radiation and chemical carcinogen is the most common case. The aim of this study is to elucidate the age dependency on the mode and mechanism of the combined effect on thymic lymphoma (TL) development after simultaneous exposure of X-rays and ENU.
Eight-week-old female B6C3F1 mice were exposed to X-rays (0.2 to 1.0 Gy per week) for 4 consecutive weeks, and the same mice were simultaneously treated with ENU (50 to 200 ppm) in drinking water.
Combination of low dose of X-rays (0.2 and 0.4Gy per fraction) and ENU (50 ppm) did not induce TL. However, combination of higher dose of X-rays (0.8 and 1.0 Gy per fraction) and ENU (100 and 200 ppm), enhanced TL development synergistically. The frequency of point mutations of Ikaros in the TL after 8-week-old treatment was much lower (18%) than that from 4-week-old (43%) (p<0.001). The frequent base substitutions, G to A, T to C, and G to T, in 4-week-old treatment were also decreased in that after 8-week-old treatment.
The results suggest that the contribution of Ikaros mutation to lymphomagenesis changes depending on age.