Abstract
The risk of cancer due to exposure to ionizing radiation is higher in infants than in adults. In a previous study, the effect of adult-onset calorie restriction (CR) on carcinogenesis in mice after early-life exposure to X-rays was examined (Shang, Y, Kakinuma, S, Yamauchi, K, et al. Cancer prevention by adult-onset calorie restriction after infant exposure to ionizing radiation in B6C3F1 male mice. Int J Cancer. 2014; 135: 1038-47). The results showed that the tumor frequency was reduced in the CR group. However, the mechanism of tumor suppression by CR is not yet clear. In this study, we examined the effects of CR on radiation-induced mutations using gpt delta mice, which are useful to analyze mutations in various tissues throughout the whole body. Infant male mice (1-week old) were exposed to 3.8 Gy X-rays and fed a control (95 kcal/week/mouse) or CR (65 kcal/week/mouse) diet from adult stage (7-weeks old). Mice were sacrificed at the age of 7 weeks, 8 weeks and 100 days, and organs (spleen, liver, lung, thymus) were harvested. Mutations at the gpt gene in the DNA from the spleen were analyzed by using a gpt assay protocol that detects primarily point mutations in the gpt gene. The results showed that mutation frequencies were decreased in CR groups compared with non-CR groups. Sequence analysis of the gpt gene in mutants revealed a reduction in the G:C to T:A transversion in CR groups. Since it is known that 8-oxoguanine could result in this base substitution and that CR has an effect of reducing oxidative stress, these results indicate that the suppression of oxidative stress by CR is the cause of the reduction of this transversion.
Highlights
Children are considered to be more highly sensitive to the carcinogenic effects of ionizing radiation than adults
We found that Calorie restriction (CR) decreased mutation frequency at the gpt gene, and suggest that the reduction in oxidative stress is responsible for the suppression of mutation frequencies
We examined the effect of adult-onset CR on the mechanisms of mutagenesis in infant-irradiated mice
Summary
Children are considered to be more highly sensitive to the carcinogenic effects of ionizing radiation than adults. CR appears to affect the initiation phase and the promotion phase of carcinogenesis These results indicate that CR is very effective in cancer prevention, CR is not appropriate for children because it might cause malnutrition. To circumvent this difficulty, the effects of adult-onset CR on carcinogenesis in mice irradiated at infant age was examined [9]. The results showed that CR reduced the risk of some tumors, e.g. hepatocellular carcinoma, late-occurring non-thymic lymphoma (TL) and lung tumor, indicating that adult-onset CR was effective in suppressing late-occurring tumors caused by childhood exposure These results suggest that CR might be an effective protocol to suppress the carcinogenic incidence even at later stages after radiation exposure. We found that CR decreased mutation frequency at the gpt gene, and suggest that the reduction in oxidative stress is responsible for the suppression of mutation frequencies
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