X Radiation Up-regulates the Occurrence and the Multiplicity of Invasive Carcinomas in the Intestinal Tract of Apcmin/+ Mice

Nakayama, T., Yamazumi, K., Uemura, T., Yoshizaki, A., Yakata, Y., Matsuu-Matsuyama, M., Shichijo, K. and Sekine, I. X Radiation Up-regulates the Occurrence and the Multiplicity of Invasive Carcinomas in the Intestinal Tract of Apcmin/+ Mice. Radiat. Res. 168, 433–439 (2007). X rays are well known to cause genetic damage and to induce many types of carcinomas in humans. The Apcmin/+ mouse, an animal model for human familial adenomatous polyposis (FAP), contains a truncating mutation in the APC gene and spontaneously develops intestinal adenomas. To elucidate the role of X rays in the development of intestinal tumors, we examined the promotion of carcinogenesis in X-irradiated Apcmin/+ mice. Forty out of 77 (52%) X-irradiated Apcmin/+ mice developed adenocarcinomas that invaded the proprial muscle layer of the small intestine; 24 of 44 (55%) were in males, and 16 of 33 (49%) were in females. In contrast, invasive carcinomas were detected in the small intestines of only 13 of 64 (20%) nonirradiated Apcmin/+ mice; nine of 32 (28%) were in males and four of 32 (13%) were in females. These differences between X-irradiated and nonirradiated Apcmin/+ mice in the occurrence of invasive intestinal carcinomas were statistically significant (P < 0.05 for males, P < 0.005 for females). In wild-type mice, invasive carcinomas were not detected in either X-irradiated or nonirradiated mice. Apcmin/+ mice had many polyps in the large intestine with or without X irradiation; there was no difference in the number of polyps between the two groups. Also, invasive carcinomas were not detected in the large intestine with or without irradiation. The occurrence of mammary tumors, which was observed in Apcmin/+ mice, was found to be increased in irradiated Apcmin/+ mice (P < 0.01). Apcmin/+ mice had many polyps in the small and large intestines with or without X irradiation. X-irradiated Apcmin/+ mice had highly invasive carcinomas in the small intestine with multiplicities associated with invasiveness. Our results suggest that X radiation may promote the invasive activity of intestinal tumors in Apcmin/+ mice.