Mouse thymic lymphomas arising after irradiation between with or without calorie restriction

Calorie restriction (CR) is known to decrease not only spontaneous but also chemical carcinogen and radiation-induced carcinogenesis. However, the biological mechanisms for the anti-cancer effect of CR remain unclear. In this study, analyzed and compared with genomic alterations in thymic lymphoma (TL) arising after irradiation between with or without CR. The frequency of point mutations at Pten locus on chromosome 19 was not different between 95 kcal and 65 kcal groups, but the frequency of LOH with DNA copy number change in 65 kcal group tended to be higher than 95 kcal group. On chromosome 4 and 11, the LOH frequency was not different between 95 kcal and 65kcal groups, but the LOH mechanism was different. In 65 kcal group, the frequency of LOH without DNA copy number change by chromosome mis-segregation or mitotic recombination was lower than 95 kcal group, but then the frequency of LOH with DNA copy number change by deletion was higher than 95 kcal group. The frequency of genomic alterations such as LOH and point mutation at Ikaros on chromosome 11 were observed as high as 70% (19 / 27) in 95 kcal group and 76% (16 / 21) in 65 kcal group. However, the mechanisms of LOH and Ikaros inactivation are different between 95 kcal and 65 kcal group. Mice were irradiated with 3.8 Gy X-rays at 1 week of age, and calorie restriction started at 7 weeks of age. Forty-eight thymic lymphomas were analyzed consisted of 27 samples obtained from normal diet group, 95 kcal/week, and 21 samples obtained from the calorie restriction group, 65 kcal/week.