Molecular nature of mutations induced by irradiation with repeated low doses of X-rays in spleen, liver, brain and testis of lacZ-transgenic mice

Purpose: To investigate the molecular characteristics of mutations induced by repeated low doses of X-rays in spleen, liver, brain and testis of mice. Materials and methods: Muta™ mice, which harbour the lacZ gene contained in the lambda genome, were irradiated with 0.15 Gy every Monday, Wednesday and Friday for 6 months starting at 10 weeks of age for a total of 78 times. Four months after the last irradiation, DNAs were isolated from the four different tissues and the mutant frequencies of lacZ were determined. Next, the nucleotide sequences of the mutant lacZ genes were determined and compared with that of the wild-type to identify the molecular changes in the mutants. The frequencies of different types of mutations were compared with those found in age-matched non-irradiated mice. They were also compared with those found in mice irradiated with a single high dose. Results: The repeated low-dose irradiation resulted in slight increases in the mutant frequency in the four kinds of tissues. The spleen, liver and brain in repeatedly irradiated mice showed higher frequencies of deletion type mutations than those of non-irradiated mice. In testis. however, the level of the increase was modest and not statistically significant. Complex type mutations were observed only in irradiated tissues. The characteristics observed in somatic tissues were similar to those induced by a single high dose of irradiation. Conclusions: The results suggest that the mechanism of mutation induction in vivo is similar between low- and high-dose irradiation in spleen, liver and brain. The low induction of deletion mutations in testis with low-dose irradiation suggests that spermatogonial cells have a unique DNA repair system against low-dose radiation-induced damage.