Abstract
It has been reported that the frequency of tumors in X-irradiated mice is dependent upon the age at exposure to radiation. Since mutation in the cancer-related genes is supposed to be one of the critical causes which lead to tumorigenesis, we analyzed the fraction of somatic mutations in vivo at the Aprt locus, encoding adenine phosphoribosyltransferase, after exposure of mice to X-rays at different ages. As the Aprt gene resides on the mouse chromosome 8, it could be a good model to analyze the mutagenesis at autosomal genes. We used mice which are heterozygous for the Aprt locus with an APRT-defective allele as well as a normal allele. Mice were irradiated at the age of either 1 week or 7 weeks, with X-rays of 1Gy once, of 4Gy once, or of 1Gy for 4 times with 1 week intervals. At the eighth week after irradiation, spleens were removed and lymphocytes were separated for the cell culture. The fraction of mutations were assessed following the microtiter plate protocol using 8-aza-adenine as the selection drug for APRT-deficient mutants. Generally speaking, lymphocytes from the mice irradiated at the age of 1 week showed increased mutant fractions to a certain extent, in contrast to the lymphocytes from mice irradiated at the age of 7 weeks which did not show any increase in the mutant fractions. These results suggest that mice irradiated at neonatal age are more sensitive to the radiation-induced mutagenesis at the autosomal loci than mice irradiated at adult age, which might have some impact on radiation-induced tumorigenesis.
