RESUMO
PURPOSE: The objective of the study was to estimate the DNA damage in blood leukocytes at long terms after irradiation of mice with carbon ions (450 MeV/nucleon) both before and in the Bragg peak. MATERIALS AND METHODS: White outbred SHK male mice were exposed to whole-body irradiation with carbon ions at doses of 0.1-2 Gy in the spread-out Bragg peak and at a dose of 6 Gy before and in the Bragg peak. At different times after irradiation (1-75 days), whole blood was collected from the tail of each mouse and analyzed by the comet assay. Mice X-irradiated in the same dose range served as a positive control. The level of the expression of mRNA of CDKN1A, APEX1, BBC3, TXN2, and ß-ACT genes in bone marrow cells was determined in animals irradiated with carbon ions at doses of 0.1-2 Gy using the real-time PCR. RESULTS: It was found that, 24 h after 12C-irradiation, a dose-dependent (0.1-2 Gy) increase in the DNA damage of leukocytes occurred, which was accompanied by a decrease in their concentration and an increase in the expression of the CDKN1A and BBC3 genes in bone marrow cells. The expression of the APEX1 and TXN2 genes did not change. In mice 12C-irradiated at a dose of 6 Gy before and in the Bragg peak, the level of DNA damage changed as follows: by day 3, it increased; by day 23 it returned to the control level; by day 30, it increased again; and by day 75, it fell to the control level on irradiation before the Bragg peak and was significantly higher (p < .05) than in the control after irradiation in the Bragg peak. CONCLUSIONS: The dynamics of changes in the level of DNA damage in leucocytes of 12C-irradiated mice within 30 days is similar to that in mice exposed to sublethal doses of X-radiation. The retention of the high level of DNA damage by day 75 after 12C-irradiation in the Bragg peak indicates a significant injury of cells from different cell pools of the blood system. The high level of DNA damage may be related not only to complex DNA injuries but also to chronic oxidative stress.