量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum and Radiological Science and Technology.
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Radiation carcinogenesis in human is considered as a result of the combined effect of radiation and environment factors. We previously showed that the combined effect on the induction of thymic lymphoma (TL) after exposure to X-rays and N-ethyl-N-nitrosourea (ENU) was dependent upon dose of carcinogen and treatment order. Considering our real life, the simultaneous exposure of radiation and chemical carcinogen is the most common case. The aim of this study is to elucidate the mode and mechanism of the combined effect on TL development after simultaneous exposure of X-rays and ENU.
Four-week-old female B6C3F1 mice were exposed to X-rays (0.2 to 1.0 Gy per week) for 4 consecutive weeks, and simultaneously treated with ENU (0, 50, 100, 200 ppm) in drinking water. Combination of low dose of X-rays (0.2 and 0.4Gy x4) and ENU (50 ppm) did not induce TL. However, in combination of higher dose of X-rays (0.8 and 1.0 Gy x4) and ENU (100 and 200 ppm), the TL development was synergistically enhanced. Molecular analysis demonstrated that the frequency of point mutations of Ikaros in the TL after simultaneous exposure was increased (43%) compared with that after single exposure of X-rays (20%) or ENU (16%).
TL induced by simultaneous exposure harbored not only mutations, which were identical with those found in TL by single exposure of ENU, but also new type of mutation such as G to T. It is concluded that synergistic effect of simultaneous exposure is ascribed, at least in part,to the increased frequency of point mutation of Ikaros.
Effect of simulataneous exposure of X-rays and N-ethyl-N-nitrosourea on lymphomagenesis in B6C3F1 mice
