Radioprotective combination of α-tocopherol and ascorbic acid promotes apoptosis that is evident by release of low-molecular weight DNA fragments into circulation

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.