Abstract
The long-lived radical produced by radiation exposure results in the delayed-type point mutation and transformation in vitro. Addition of vitamin C (VC) just after irradiation reduces the frequencies of point mutation and transformation. The data on the role of long-lived radical in radiation carcinogenesis in vivo are insufficient. In this experiment, we investigated an involvement of long-lived radical in radiation-induced mouse lymphomagenesis. We determined the effect of VC on incidence of thymic lymphoma (TL) and the mutation pattern of cancer-related genes in them.
Four-weeks old female B6C3F1 mice were exposed to X-rays (1.4 Gy per week) for 4 consecutive weeks. VC derivative sodium-L-ascobyl-2-phosohate, which shows long half-life in vivo, was used as anti-radical agent (100 mg / kg). Three experimental groups were set, (i) irradiation alone (X-rays), (ii) irradiation followed by VC just after X-rays (X+VC) and (iii) (X+VC) with additional VC treatment for subsequent three months (X+VC continue). We analyzed the gene expression, the point mutation, and the protein expression of tumor suppressor gene Ikaros to which mutation pattern was clarified in radiation-induced TL.
Latent period was shortened in (X +VC) group, but extended in (X+VC continue) group, compared to X-rays group. Interestingly, the latter group lacked point mutation, but not aberrant splicing, of Ikaros. These results suggest an involvement of long-lived radical in radiation-induced lymphomagenesis.
