Late Effects of γ, n-Irradiation of Mice: Shortening of Telomeres and Tumors Development

Abstract

Purpose: To investigate the telomere length (TL) of bone marrow and thymus cells as a marker of replicative aging late after the prolonged γ, n-irradiation of mice at low and moderate doses and analysis of the appearance of tumors by the end of the experiment − after 14 months. Material and methods: C57Bl/6 and CBA mice were irradiated at doses of 10–500 mGy at the OR-M facility using Pu-Be radionuclide sources at a total absorbed dose rate of neutrons and gamma rays of 2.13 mGy/h, 75 % of which – 1.57 mGy/h – accounted for neutrons with an average energy of 3.5 MeV. Absolute TL in bone marrow and thymus cells was determined using real-time PCR 2 months and 1 year 2 months after irradiation, and the mean TL was calculated. Tumors found during the mice organs examination after autopsy were subjected to histological examination. Results: It was shown that the TL in bone marrow and thymus cells of control CВA mice was 2 times higher than the TL observed in C57Bl/6 mice. Prolonged γ, n-irradiation of C57Bl/6 mice led to a dose-dependent decrease in TL in bone marrow cells 14 months after exposure, which was statistically significant at doses of 100 and 500 mGy. A decreased TL in the thymus was found only at a dose of 500 mGy. During this period, TL in bone marrow cells of CBA mice was reduced in dose-independent manner, starting from as low as 10 mGy, but no statistically significant decrease in TL was found in the thymus. The results obtained indicate the acceleration of replicative senescence of bone marrow cells in mice in the long term period after γ,n-irradiation already at low doses, and in thymus cells only at a dose of 500 mGy. Twenty-four hours after irradiation at doses of 100 and 500 mGy the number of leukocytes in mice of both lines was reduced, which was recovered in C57Bl/6 mice after a week, and in CBA mice – after two weeks. In 14 months after γ, n-irradiation, the appearance of tumors was found in mice of both studied lines: in CBA mice, lung adenocarcinoma at a dose of 50 mGy (in 1 out of 10) and uterine carcinosarcoma at a dose of 500 mGy (in 1 out of 10); in C57Bl/6 mice, keratinizing squamous cell carcinoma of the uterus at a dose of 500 mGy (2 out of 10) was seen in the absence of tumors in control mice. Histological examination of the liver of CBA mice after γ, n-irradiation at a dose of 500 mGy revealed deep dystrophic changes, the causes of which are not clear. Conclusion: The results obtained indicate a high biological hazard of prolonged γ, n-irradiation at doses above 10 mGy, since after irradiation at this dose, an acceleration of replicative senescence of bone marrow cells in the long-term period was found, and the possibility of tumor formation increases after irradiation at a dose of 50 mGy and higher.