title: Radioprotective combination of α-tocopherol and ascorbic acid promotes apoptosis that is evident by release of low-molecular weight DNA fragments into circulation.
abstract: OBJECTIVE
  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.
  
  
  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.affiliation: a N. N. Petrov Research Institute of Oncology, Ministry of Public Health , St. Petersburg.|b International Research Center 'Biotechnologies of the Third Millennium' ITMO University 191002 , St. Petersburg , Russia.
authors.forename: Irina
authors.initials: I
authors.lastname: Vasilyeva
authors.affiliation: a N. N. Petrov Research Institute of Oncology, Ministry of Public Health , St. Petersburg.|b International Research Center 'Biotechnologies of the Third Millennium' ITMO University 191002 , St. Petersburg , Russia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Bespalov
authors.affiliation: c Center for the Study of Chronic Metabolic Diseases, School of Systems Biology, College of Science, George Mason University , Fairfax , VA , USA.|d Moscow Institute of Physics and Technology , Dolgoprudny , Moscow Region.|e Federal State Budgetary Institution 'Research Centre for Medical Genetics' under the Russian Academy of Medical Sciences , Moscow , Russia.
authors.forename: Ancha
authors.initials: A
authors.lastname: Baranova
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects*; D001205:Ascorbic Acid / Q000008:administration & dosage*; D001854:Bone Marrow Cells / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D002478:Cells, Cultured; D004247:DNA / Q000097:blood; D053938:DNA Fragmentation / Q000528:radiation effects*; D004338:Drug Combinations; D008297:Male; D008970:Molecular Weight; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D014815:Vitamins / Q000008:administration & dosage; D024502:alpha-Tocopherol / Q000008:administration & dosage*
chemical_list: D004338:Drug Combinations; D011837:Radiation-Protective Agents; D014815:Vitamins; D004247:DNA; D024502:alpha-Tocopherol; D001205:Ascorbic Acid
keywords: LMW DNA; apoptosis; ascorbic acid; radioprotectors; α-tocopherol