@misc{oai:repo.qst.go.jp:00069755,
 author = {Amasaki, Yoshiko and Hirano, Shinobu and Yamauchi, Kazumi and Nishimura, Mayumi and Imaoka, Tatsuhiko and Shimada, Yoshiya and Kakinuma, Shizuko and 甘崎 佳子 and 坂入 しのぶ and 山内 一己 and 西村 まゆみ and 今岡 達彦 and 島田 義也 and 柿沼 志津子},
 month = {May},
 note = {Purpose
Radiation carcinogenesis in human is considered as a result of the combined effect of radiation and environment factors. This study aimed to elucidate the mode and mechanism of the combined effect on thymic lymphoma development after simultaneous exposure of X-rays and N-ethyl-N-nitrosourea (ENU). 
\nMethods
Four and eight-week-old female B6C3F1 mice were simultaneously exposed to X-rays (0.2 to 1.0 Gy per week) and ENU (50 to 200 ppm) in drinking water for 4 consecutive weeks for the induction of thymic lymphomas.  Ikaros alteration in lymphomas was analyzed by RT-PCR, DNA sequencing and Western blotting.
\nResults
Combination of low dose of X-rays at dose less than 0.4 Gy per fraction and ENU at 50 ppm did not induce lymphomas. In contrast, combination at higher dose of X-rays and ENU enhanced lymphoma development synergistically. Ikaros is tumor suppressor gene, which is frequently altered in lymphomas by point and frameshift mutations, alternative splicing, transcriptional silencing.  The frequency of total Ikaros alteration in the lymphomas after 4-week- and 8-week-old treatment was 50% and 30%, respectively. Among these, point mutation made up 43% and 18%, respectively.  The base substitutions of T to C and G to A/T mostly contributed.  Interestingly, G to A/T was identified in only lymphomas induced by combined exposure started at 4-week-old.
\nConclusion 
Simultaneous exposure to X-rays and ENU enhanced T to C base substitution, and generated new types of G to A/T.  The Ikaros point mutation appeared to be affected by the age-at-exposure., 2nd Asian Congress of Radiation Research (ACRR2009)},
 title = {Detailed analysis of Ikaros mutation in mouse thymic lymphoma induced by simultaneous exposure of X-rays and N-ethyl-N-nitrosourea},
 year = {2009}
}