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.

Keywords:

• α-tocopherol
• ascorbic acid
• radioprotectors
• LMW DNA
• apoptosis

Acknowledgements

The authors are grateful to their host institutions for unwavering support.

Declaration of interest

The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

LMW DNA extraction and analysis (A. Baranova) was supported by the Project No. RFMEFI60714X0098 (Ministry of Science and Education, Russia). This work was also supported by the Government of Russian Federation Grant 074-U01.