Radiation carcinogenesis in human is considered as a result of the combined exposure with other environment factors. The aim of this study is to examine the mechanism of thymic lymphomagenesis induced by combined exposure of radiation and chemical carcinogen. We investigated frequency and spectrum of the mutation, and an expression of repair genes after combined exposure of X-rays with N-ethyl-N-nitrosourea (ENU).B6C3F1gpt-delta transgenic mice were exposed to X irradiation at 0.2 or 1.0 Gy for consecutive 4 weeks, followed by ENU at 200ppm for 4 weeks. Four weeks after the end of ENU treatment, genome DNA was prepared from thymus and determined the mutation frequency and spectrum in gpt gene. The expression of Mgmt and other repair genes during ENU treatment was examined by Real Time PCR or RT-PCR array. We previously reported that irradiation with 0.2 Gy suppressed ENU-induced thymic lymphomagenesis while that with 1.0 Gy enhanced. This study showed that exposure to 0.2Gy dramatically suppressed mutation induction by ENU, especially G to A transition. When combined with 1.0 Gy, mutant frequency was enhanced by 30-folds and accelerated clonal expansion of mutated cells. The expression of Mgmt after exposure of 0.2Gy resulted in a higher expression than that after ENU alone at the initial one week, but increase was smaller thereafter. Other candidate repair genes are now investigated by Real Time PCR Array.1st Asian Conference on Environmental Mutagens, 36th Annual Meeting of the Japanese Environmental Mutagen Societ
