@misc{oai:repo.qst.go.jp:00070829,
 author = {Amasaki, Yoshiko and Hirano, Shinobu and Shang, Yi and Sawai, Tomoko and Nishimura, Mayumi and Shimada, Yoshiya and Kakinuma, Shizuko and 甘崎 佳子 and 坂入 しのぶ and 尚 奕 and 澤井 知子 and 西村 まゆみ and 島田 義也 and 柿沼 志津子},
 month = {Jul},
 note = {Introduction
Radiation carcinogenesis in human is considered as a result of the combined effect with other environmental carcinogens such as tobacco and foodstuffs. We previously showed that single exposure to X-rays or N-ethyl-N-nitrosourea (ENU) at high dose efficiently induced thymic lymphoma (TL) and that loss of heterozygosity (LOH) on chromosome 11, which accompanied altered expression and mutation of Ikaros, was characteristic to X-ray-induced TL (>40%), while it was rarely observed in ENU-induced ones. In addition, the combined effect of two carcinogens on the induction of TL depended upon not only the dose of carcinogen(s) but also the order of treatment. The aim of this study was to clarify the effect of the interval between X-rays and ENU on the TL induction and its underlying mechanism.
Materials and methods    
Fifty of 4-week-old female B6C3F1 mice were used in each group. They were exposed to X-rays (1.0 Gy per fraction) for four consecutive weeks, and then were treated with ENU (200 ppm) in drinking water for 4 weeks with the interval of 0, 2, 4, and 8 weeks. The mice were observed until moribundity. Lifespan, incidence of TL and LOH frequency of chromosome 11, together with that of chromosomes12 and 19, were determined. 
Results and discussion 
1. Lifespan of the groups with the treatment interval of 0 or 2 weeks were significantly shorter than that with the interval of 4 or 8 weeks, indicating a significant interaction of the two carcinogens with shorter interval. 
2. Incidence of TL after X-irradiation alone was 13%, and that after ENU treatment was around 20% regardless of the age at exposure. The incidences of TL of the groups with the interval of 0, 2, 4, and 8 weeks were 94%, 98%, 58%, and 70%, respectively.  Thus, the effect of prior X-irradiation persisted up until 8 weeks, but longer interval was much less effective than shorter one. 
3. LOH frequency on chromosome 11 was low for the group with no interval (15%), suggesting less involvement of X-ray-associated LOH in TL induction. However, spit of the two treatments longer than 2 weeks increased the LOH frequency to the level of X-irradiation alone (35-45%). LOH frequencies on chromosomes 12 and 19, however, were little affected by the presence of interval.
Conclusion
The interval period between X-rays and ENU was critical for both the frequency of TL and the mechanism of lymphomagenesis involving LOH on chromosome 11, possibly Ikaros mutation., The 22nd Biennial Congress of the European Association for Cancer Research},
 title = {Molecular interaction of X-rays and N-ethyl-N-nitrosourea in thymic lymphomagenesis depends on the interval of two treatments},
 year = {2012}
}