Immuno-Therapy, Radiation Protection, Medical management, Antioxidants, Antiradiation Vaccine, Radiation.

1. Medical Management of Acute
Radiation Syndromes : Comparison
of Anti-Radiation Vaccine and
Antioxidants radioprotection
potency.
Dmitri Popov. PhD, Radiobiology.
MD (Russia)
Advanced Medical Technology and Systems Inc. Canada.
Slava Maliev, PhD, Radiobiology,
Academy of Science, Russia.

2. Medical Management of Acute Radiation
Syndromes.
 This experimental study of biological effects of the Antiradiation Vaccine and
Antioxidants were studied.
 Antiradiation Vaccine and Antioxidants were used for prophylaxis and
treatment of the Acute Radiation Syndromes caused by high doses of the low-
LET radiation.

3. Medical Management of Acute Radiation
Syndromes
 An antioxidant is a molecule that inhibits the oxidation of other molecules.
 Oxidation is a chemical reaction involving the loss of electrons or an increase
in oxidation state. Oxidation reactions can produce free radicals. In turn,
these radicals can start chain reactions.
 When the chain reaction occurs in a cell, it can cause damage or death to the
cell. Antioxidants terminate these chain reactions by removing free radical
intermediates, and inhibit other oxidation reactions.

4. Medical Management of Acute Radiation
Syndromes.
 Although oxidation reactions are crucial for life, they can also be damaging;
plants and animals maintain complex systems of multiple types of
antioxidants, such as glutathione, vitamin C, vitamin A, and vitamin E as well
as enzymes such as catalase, superoxide dismutase and various peroxidases.

5. Medical Management of Acute Radiation
Syndromes.
 Antioxidant supplementation during radiation therapy poses a conundrum for
the radiation oncologist, as antioxidants that protect normal cells from
reactive oxygen species may provide the same benefits to cancer cells and
reduce the efficacy of treatment. Short- and long-term injury to healthy
cells, including tissue damage and increased risk of oncogenic transformation
, can be prevented by antioxidants, as seen experimentally. New findings that
antioxidants induce apoptosis in cancer cells and protect patients from
painful side effects of radiation treatment may prove these compounds useful
in future adjuvant therapy. Carmia Borek, 2004.
 Some scientists offering antioxidants as a effective method of therapy for
Acute Radiation Disease vs Acute Radiation Syndromes.

6. Medical Management of Acute Radiation
Syndromes.
 Toxicology. 2003 Jul 15;189(1-2):1-20.
 Protection against ionizing radiation by antioxidant nutrients and
phytochemicals.
 Weiss JF1, Landauer MR.
 The potential of antioxidants to reduce the cellular damage induced by
ionizing radiation has been studied in animal models for more than 50 years.
The application of antioxidant radioprotectors to various human exposure
situations has not been extensive although it is generally accepted that
endogenous antioxidants, such as cellular non-protein thiols and antioxidant
enzymes, provide some degree of protection. This review focuses on the
radioprotective efficacy of naturally occurring antioxidants, specifically
antioxidant nutrients and phytochemicals, and how they might influence
various endpoints of radiation damage.

7. Medical Management of Acute Radiation
Syndromes.
 An important role of Reactive Oxygen Species (Singlet oxygen, hydroxyl
radicals, superoxide anions and bio-radicals) in development of the Acute
Radiation Syndromes could be defined as a "central dogma" of radiobiology.
 Is it true ?
 Partially Yes. But ROS is not only alone major mechanism of pathology of
Acute Radiation Disease.

8. Medical Management of Acute Radiation
Syndromes.
 Oxidation and damages of lipids, proteins, DNA, and RNA are playing active
role in development of post-radiation apoptosis.
 However, the therapeutic role of antioxidants in modification of a post-
radiation injury caused by high doses of radiation remains controversial.
 Previous studies have had revealed that antioxidants did not increase a
survival rate of mammals with severe forms of the Acute Radiation Syndromes
caused by High Doses of the low-LET radiation.
 Some studies showed that antioxidants nutrients used as for treatment of ARS
could even increase the mortality rate after high doses of radiation.

9. Medical Management of Acute Radiation
Syndromes.
 Anti-radiation Vaccine(ARV) contains toxoid forms of the Radiation Toxins(RT)
from the Specific Radiation Determinants Group (SRD).
 The RT SRD posses toxic and antigenic properties at the same time and
stimulates a specific antibody elaboration and humoral response form
activated acquired immune system.

10. Medical Management of Acute Radiation
Syndromes.
 We compare two different methods of treatment and prophylaxis of Acute
Radiation Syndrome.
 Antioxidants treatment and prophylaxis of ARS.
 Immunotherapy and prophylaxis of ARS.

11. Medical Management of Acute Radiation
Syndromes.
 The blocking anti-radiation antibodies induce an immunologically specific
effect to radiation toxins and posses inhibiting effects on radiation neuro-
toxicity, vascular-toxicity, gastrointestinal toxicity, hematopoietic toxicity,
and radiation induced cytolysis of selected groups of cells which are sensitive
to radiation.

12. Medical Management of Acute Radiation
Syndromes.
 Methods and materials:
 Scheme of experiments:
 1. Irradiated animals with development of Cerebrovascular ARS (Cv-ARS),
Cardiovascular ARS (Cr-ARS) Gastrointestinal ARS(GI-ARS), Hematopoietic ARS (H-
ARS) -control - were treated with placebo administration.
 2. Irradiated animals were treated with antioxidants prophylaxisis and
antioxidants treatment of Cv-ARS, Cr-SRS, GI-ARS, Hp-ARS forms of the ARS.
 3. irradiated animals were treated with radioprotection by Antiradiation Vaccine
against CV-ARS, Cr-ARS, GI -ARS, Hp-ARS forms of the ARS.
 4. Irradiated animals were treated with development of Cr -ARS, Cv-ARS, GI -ARS
and Hp -ARS forms of the ARS -Combined administration of the Antiradiation
Vaccine and Antioxidants used for radiation protection and treatment.

13. Medical Management of Acute Radiation
Syndromes.
 Equipment for irradiation: 60 Cobalt Facility : "Panorama", "Puma".
 Exposure rate: o.6 Gy/min.
 During experiments, animals received the whole-body irradiation in a single
dose. The radiation doses varied in a range from 7.5 Gy up to 10 Gy.
 These experiments were accomplished at the radio-biology department of
Moscow State Academy of Veterinary Medicine.

14. Medical Management of Acute Radiation
Syndromes.
 Radio-protectants:
 1. Antioxidants :
 The Antioxidant mixture contained Coenzyme Q10, Vitamin A(retinol),
Vitamin C(ascorbic acid), natural beta-carotene, d-alphatocopherol succinate,
d-alpha tocopherol acetate.
 The antioxidants mixture was prepared in a powder form.
 Method of administration: oral administration by gavage.
 The doses of antioxidants varied from 100 mg/kg up to 500 mg/kg.

15. Medical Management of Acute Radiation
Syndromes.
 2. Placebo:
 Method of administration: oral ad-ministration by gavage. Five days daily
before and after the whole-body gamma-irradiation.
 3. Antiradiation Vaccine (ARV) contained toxoid (inactivated) forms of
radiomimetics -Neurotoxins SRD-1; SRD-2; SRD-3 and Hematotoxins SRD-4.
 Method of administration ARV: intramuscular or subcutaneous,24 days before
irradiation.
 Animals: 15 Sheep – 5 sheep for each group, 50 rabbits – group 1 – 16 rabbits,
group 2 – 16 rabbits and group 3 – 18 rabbits .

16. Medical Management of Acute Radiation
Syndromes.
 Results:
 The results of oral administration of antioxidants mixture provided before and
after the whole-body high doses of gamma-irradiation demonstrated that
survival rate was similar to placebo group -all animals died in first 5-10 days
after irradiation.
 Radioprotection activity did not depend on the doses of the antioxidants
preparation and seams that high doses of antioxidants administered before
and after irradiation were even harmful. Comparing to the placebo group, the
group with antioxidants pre-treatment and treatment had demonstrated a
shorter life time after irradiation. The Group received the radioprotection
with the Antiradiation Vaccine had demonstrated high survival rate -60% at
severe form of Cerebrovascular ARS.

17. Medical Management of Acute Radiation
Syndromes.
 Summary and conclusions: 1. Antioxidants are not effective radio-protectants
or therapeutic agents at severe and extremely severe forms of Acute
Radiation Syndromes.
 2. High doses of antioxidants, administered orally, 7 days before(dd)
irradiation could be a factor which increased the lethality rate and decreased
life time even comparing with the placebo group.
 3. The Anti-radiation Vaccine is an effective radio-protectant with 60-70% of
survival rate at LD 100/30 doses of irradiation and severe forms of the ARS.
4.Combined administration of the Anti-radiation Vaccine (I/M) and
antioxidants (Per os) could be useful even though the survival rates were
similar to results with immuno-prophylaxis by Anti-radiation Vaccine alone.
The group of irradiated animals with combined administration had
demonstrated a better clinical picture and a shorter period of stage of
recovery following after irradiation.