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Radiation Oncology Research
Published Articles and Abstracts
Protective effects of Poly-MVA during Radiation
Exposure
Click on each Graphic below
to review research
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(1)
"DNA Reductase: A Synthetic Enzyme with
Opportunist Clinical Activity Against Radiation Sickness"
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(2)
Protection from gamma-radiation insult to antioxidant defence
and cellular DNA by POLY-MVA.....
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(3)
Radiation Protection by
Alpha-Lipoic Acid-Palladium
Nanoparticle Complex
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(4)
Poly MVA as a
Radioprotector in
Radiotherapy
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(1)
"DNA Reductase: A Synthetic Enzyme
with Opportunist Clinical Activity Against Radiation Sickness"
(Garnett and Remo, International Symposium on
Applications of Enzymes in Chemistry, 2001)
May 2001
Plenary Session Abstracts
Merrill Garnett and John L. Remo
Garnett McKeen Laboratory, Inc., Islip, New York
DNA reductase(Poly-MVA - LAPd complex), a stable synthetic enzyme, gives protection against radiation illness. During oral administration of this material in the emergency treatment of certain brain tumors, it was found that patients
receiving concurrent radiation did not develop the usual signs of radiation toxicity such as nausea, exhaustion,
disorientation, and depression.
This compound is a liquid crystal polymer composed of palladium and lipoic acid. It has been reported to show DNA
electronic reducing activity by cyclic voltammetry. The functional catalytic group incriminated by ESR spectroscopy
is a sequestered peroxide within the polymer, which unlike solvated peroxide, does not form superoxide. We believe
this sequestered peroxide is the charge carrier site.
This compound is a liquid crystal
polymer composed of palladium and lipoic acid. It has been reported to show DNA electronic reducing activity by cyclic voltammetry (1).
A charge transfer from membrane
phospholipid to DNA is the presumptive mechanism whereby certain tumors, protozoa, and yeasts, are inhibited by
this complex. The subcellular site of destruction has been shown to be the membrane (2). The functional catalytic group incriminated by ESR
spectroscopy is a sequestered peroxide within the polymer, which unlike solvated peroxide, does not form superoxide.
We believe this sequestered peroxide
is the charge carrier site.
This charge carrier is able to
discharge into tumor membranes during cellular migration of the complex. The electronic reduction denatures the
polar disulfide groups binding peptides together and compromises the integrity of the membrane.
Fluorescent probes delineate
the increase in cell voltage,
and the membrane rupture. This
is seen in the facultative protozoan Tetrahymena. While Tetrahymena tolerates DNA reductase under aerobic conditions,
it suffers membrane rupture in a similar challenge under anaerobic conditions.
Another illustration of this principle occurs when sea urchins
are exposed to DNA reductase. Only
those cells in the anaerobic archenteron are destroyed. This produces sea urchins without a gastro-intestinal system. In normal cells, the absence of side effects is attributed to the process by which
reducing equivalents are rapidly engaged in electron transfer sequences which terminate in oxygen.
This textbook metabolic differential protects
the host organism and its energy competent cells from electrocution.
This is the proposed explanation as to why formal studies in mice, and twenty documented human cases testify to
the safety of synthetic DNA reductase. It was
during the emergency clinical use of orally administered DNA reductase that we learned of its protection against
the side effects of radiation.
There was both prevention and relief from radiation
sickness occurring in patients receiving radiation therapy. Subsequent questioning in more radiated patients indicated this protection was reproducible. We
believe the mechanism of the radiation protection by DNA reductase will be found in studies of the vector addition
radiative and non-radiative charge transfer at the level of its liquid crystal structure.
While radiation protection was not the original therapeutic design for DNA reductase, it appears that quantitative
animal and human studies in this are warranted.
Critical assays of the dose relationships can develop this material for applications in radiation risk environments
in civilian utilities, and military sites. Such studies can lead to commercial development and an advance in public
safety procedures.
References:
1. Garnett, M., U.S. Patent no. 5,463,093, Oct. 31, 1995.
2. Garnett, M., J. Inorg. Biochem. 59: nos. 2&3, C48, p.231, Elsevier, 1995.
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(2)
Protection from gamma-radiation insult to antioxidant defence and cellular DNA
by POLY-MVA, a dietary supplement containing palladium-lipoic acid formulation
Authors: Menon, Aditya1; Krishnan, Chirakkal V.2;
Nair, Cherupally Krishnan Krishnan3
International Journal of Low Radiation
Volume 6, Number 3, 11 October 2009 , pp. 248-262(15)
Document Type:
Research article
DOI:
10.1504/IJLR.2009.028892
Address:
Amala Cancer Research Centre, Thrissur 680555, Kerala, India. ' Garnet McKeen Laboratory Inc., Bohemia, NY 11716-1735,
USA; Department of Chemistry, University at Stony Brook, NY 11794–3400, USA. ' Amala Cancer Research Centre, Thrissur
680555, Kerala, India
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Abstract
(3)
RADIATION PROTECTION BY
ALPHA-LIPOIC ACID-PALLADIUM NANOPARTICLE COMPLEX
Jumitha Jayan, Lakshmy R , and Cherupally Krishnan
Krishnan Nair
Amala Cancer Research Centre, Thrissur- 680555, Kerala, India.
Background: Most of the toxic effects of acute ionizing radiation are due to increased flux of free radicals,
occurring almost instantaneously after irradiation. An ideal radioprotector is expected to prevent accumulation
of free radicals and decrease the load of reactive oxygen species to a level manageable by the inherent antioxidant
system. a- Lipoic acid (LA) is proved to be a potent free radical scavenger and metal chelator and is also responsible
for the regeneration of active forms of other cellular antioxidants. The present investigation is focused on the
enhancement in antioxidant and radioprotecting properties of LA when complexed to palladium nanoparticles.
Materials and Methods: LA (100 mM) was sonicated in the presence of 1% Pluronic F-127 and
palladium nanoparticles (0.1%). The pale solution obtained was centrifuged so that the bigger particles can be
effectively separated. The supernatant, containing the complex of LA-palladium nanoparticle (LA-Pd) was analyzed
for its radioprotecting properties in vivo. Swiss albino mice, 6-8 weeks old were whole body irradiated at different
radiation doses using a 60Co- Theatron Phoenix teletherapy unit (Atomic energy ltd, Ottawa, Canada) at a dose rate
of 1.88Gy per minute. The animals were administered with the complex orally.
Results and Discussion: The complex minimized the depletion of cellular antioxidant levels in 4 Gy  - irradiated mice and improved the percentage survival of animals exposed to a lethal dose of 10 Gy -
radiation. There was also recovery from radiation
induced body weight loss in the survivors.
Conclusions: The complexing
of the palladium nanoparticles to a- Lipoic acid significantly increased the radioprotecting property as compared to the the unbound a- Lipoic acid.
Acknowledgements: The authors are grateful to Mr. O. D. Jayakumar and Dr. Tyagi, BARC, Mumbai, for providing the
Pd nanoparticles.
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Abstract
(4)
POLY MVA AS A RADIOPROTECTOR IN RADIOTHERAPY
Aditya Menon1, Chirakkal V. Krishnan2, 3 and Cherupally Krishnan Krishnan Nair1
1Amala Cancer Research Centre, Amalanagar, Thrissur-680 555.
2Garnett McKeen Inc., Bohemia, NY 11716-1735, USA
3Department of Chemistry, University at Stony Brook, NY 11794-3400, USA
Background: Exposure to ionizing radiation causes disruption of the pro-oxidant/antioxidant balance in normal
tissues leading to protein, lipid and DNA oxidation. Compounds which can reduce damages caused by free radicals
could be useful as radioprotectors. Development of an effective non toxic radioprotector is of prime importance
in the field of radiotherapy, space flight, nuclear medicine and emergencies. The effect of the dietary supplement,
POLY MVA, containing palladium a-lipoic acid complex as the active ingredient, was examined for its use as an adjuvant
in preclinical radiation therapeutic situations in a murine model.
Materials and Methods: Swiss albino mice bearing solid tumor on hind limbs were administered
with POLY MVA (2ml/kg body weight) and exposed to whole body 4 Gy gamma-irradiation............continuing the drug
administration for 5 consecutive days. For cellular DNA repair studies, after exposure of mice to 4 Gy gamma-radiation,
POLY MVA was administered and alkaline single cell gel electrophoresis (comet assay) was performed on peripheral
blood leukocytes and bone marrow cells taken at various intervals.
Results and Discussion: Administration of POLY MVA enhanced
DNA repair in peripheral blood leukocytes and bone marrow cells of the radiation exposed mice as can be inferred from the rate of post irradiation decrease of
the comet parameters. Thus, the studies on DNA repair suggest the possible application of POLY MVA in radiotherapy scenarios.
Conclusions: Previous studies
have elucidated that POLY MVA protected cellular DNA from lethal doses of gamma radiation and could improve the
survival expectancy of irradiated animals,
possibly due to restoration of cellular antioxidants (Menon et al 2009; Int.J.Low Radiat. 6, 248-262.). The present
study revealed that the administration
of POLY MVA enhanced the DNA repair in blood leukocytes and bone marrow cells.
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PDF of all 5 Radiation Studies
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