Minマウス消化管における放射線発がん機構の解析

To elucidate the molecular mechanism of radiation tumorigenesis in mice, we generated a mouse strain by substituting an entire chromosome 18 in B6-Min mouse. The strain shows marked increase in intestinal tumors when irradiated at 2-weeks old, while there was almost no excess induction in 7-weeks-old irradiation. To clarify the mechanisms of the age dependency, we performed systemic LOH analysis of chromosome18 in the tumors. Marked difference was found in LOH patterns of spontaneous and radiation-induced tumors; tumors in 2-weeks irradiation group showed intrachromosomal LOH and copy number reduction in the Apc region, while spontaneous tumors showed whole-chromosome loss without copy number reduction. Some tumors in 7-weeks irradiation group showed LOH patterns typically seen in 2-weeks group. This suggests that X-ray exposure had induced DNA lesions in the tumors, presumably in latent form. To test the possibility, we irradiated mice, and with some intervals, administered 1% Dextan Sulfate Sodium (DSS). The combination of X-ray and DSS treatment gave synergistic effects on the colon tumor induction. Possible mechanism of the age dependency will be proposed.第69回日本癌学会学術総