Abstract
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 in the Apc gene, we developed an algorithm and parameters, using statistical programming language R, that improve the power and accuracy of LOH detection with SSLP markers. Using the algorithm and parameters, we examined for the presence or absence of LOH throughout the whole chromosome 18. The results showed 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.
