Host: The Japan Radiation Research Society
Co-host: City of Kitakyushu, University of Occupational and Environmental Health, Japan
To elucidate the molecular mechanism in radiation tumorigenesis in mice, we generated a mouse strain by substituting an entire chromosome18 in B6-Min mouse. The consomic-Min mouse strain is highly susceptible to radiation tumorigenesis; mice exposed to 2.0 Gy of X-rays at 2 weeks of age induced 7-fold small intestinal tumors and 29-fold colonic tumors over the unirradiated mice. The enhancement depended on the age at exposure; mice exposed at 7 weeks of age had lost the susceptibility to the radiation tumorigenesis. Radiation-induced colonic tumors exhibited higher frequency of allele loss in the Apc gene compared to the spontaneous tumors, while no such difference was observed for the small intestinal tumors. To clarify the molecular events leading to the allele loss of the Apc gene, we developed an algorithm and parameters, using statistical programming language R. Detailed LOH analysis spanning the entire chromosome 18 revealed that the vast majority of the radiation-induced intestinal tumors exhibited intra-chromosomal recombination, while spontaneous tumors showed entire loss of the chromosome 18 without any sign of the recombination. In all the cases mentioned above, normal allele of the Apc gene had been lost. Preliminary analysis of the Apc gene copy number suggested that spontaneous tumors retained two copies of the Apc gene, whereas a half of the radiation-induced tumors had only one copy of the Apc gene. Possible mechanism leading to the Apc inactivation will be discussed.
