Irina Vasilyeva1,2, Vladimir Bespalov1,2, Ancha Baranova3,4,5. 1. a N. N. Petrov Research Institute of Oncology, Ministry of Public Health , St. Petersburg. 2. b International Research Center 'Biotechnologies of the Third Millennium' ITMO University 191002 , St. Petersburg , Russia. 3. c Center for the Study of Chronic Metabolic Diseases, School of Systems Biology, College of Science, George Mason University , Fairfax , VA , USA. 4. d Moscow Institute of Physics and Technology , Dolgoprudny , Moscow Region. 5. e Federal State Budgetary Institution 'Research Centre for Medical Genetics' under the Russian Academy of Medical Sciences , Moscow , Russia.
Abstract
PURPOSE: Genotoxic stresses, including irradiation, lead to the apoptosis of damaged cells and the release of DNA fragments into circulation. Both α-tocopherol acetate and ascorbic acid possess antioxidant and radioprotective properties. Interestingly, depending on a particular experimental system, the treatment with vitamins may demonstrate either apoptosis-promoting or apoptosis-suppressing effects. MATERIALS AND METHODS: Adult Wistar male rats received total body irradiation with 2-100 Gy doses, while non-irradiated rats served as controls. Oral gavages with vitamins were administered either 10 min or 1 h before irradiation. Control groups were similarly treated with water. Blood samples were collected at 5 h post irradiation. The levels and the composition of circulating DNA were profiled. Chromosomal aberrations were assessed 24 h after irradiation. RESULTS: A substantial dose-dependent increase in circulating low-molecular weight (LMW) DNA levels was observed after whole body irradiation. An order-of-magnitude increase in the proportion of bone marrow cells with chromosomal abnormalities was observed after irradiation at 2 Gy. Single vitamin preparations were not protective, while the combination of α-tocopherol (10 mg/kg) and ascorbic acid (20 mg/kg) displayed a protective effect evident from marked decrease in chromosomal aberrations. In animals treated with a combination of the vitamins only, substantial increases in the release of LMW DNA were observed. CONCLUSIONS: Radioprotective combination of α-tocopherol and ascorbic acid promotes apoptosis that is evident by release of low-molecular weight DNA into circulation. We hypothesize that the pretreatment with vitamins provides radioprotection, at least in part, by aiding non-inflammatory, apoptotic elimination of most damaged cells. The microevolutionary nature of observed adaptive response provides mechanistic foundation for the phenomenon of hormesis.
PURPOSE: Genotoxic stresses, including irradiation, lead to the apoptosis of damaged cells and the release of DNA fragments into circulation. Both α-tocopherol acetate and ascorbic acid possess antioxidant and radioprotective properties. Interestingly, depending on a particular experimental system, the treatment with vitamins may demonstrate either apoptosis-promoting or apoptosis-suppressing effects. MATERIALS AND METHODS: Adult Wistar male rats received total body irradiation with 2-100 Gy doses, while non-irradiated rats served as controls. Oral gavages with vitamins were administered either 10 min or 1 h before irradiation. Control groups were similarly treated with water. Blood samples were collected at 5 h post irradiation. The levels and the composition of circulating DNA were profiled. Chromosomal aberrations were assessed 24 h after irradiation. RESULTS: A substantial dose-dependent increase in circulating low-molecular weight (LMW) DNA levels was observed after whole body irradiation. An order-of-magnitude increase in the proportion of bone marrow cells with chromosomal abnormalities was observed after irradiation at 2 Gy. Single vitamin preparations were not protective, while the combination of α-tocopherol (10 mg/kg) and ascorbic acid (20 mg/kg) displayed a protective effect evident from marked decrease in chromosomal aberrations. In animals treated with a combination of the vitamins only, substantial increases in the release of LMW DNA were observed. CONCLUSIONS: Radioprotective combination of α-tocopherol and ascorbic acid promotes apoptosis that is evident by release of low-molecular weight DNA into circulation. We hypothesize that the pretreatment with vitamins provides radioprotection, at least in part, by aiding non-inflammatory, apoptotic elimination of most damaged cells. The microevolutionary nature of observed adaptive response provides mechanistic foundation for the phenomenon of hormesis.
Authors: Irina N Vasilyeva; Vladimir G Bespalov; Alexander L Semenov; Denis A Baranenko; Valery N Zinkin Journal: Noise Health Date: 2017 Mar-Apr Impact factor: 0.867