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DNA Reductase: A Synthetic Enzyme with Opportunist Clinical Activity Against Radiation Sickness
International Symposium on Applications of Enzymes in Chemical and Biological Defense, Plenary Session Abstracts, May 2001


Merrill Garnett and John L. Remo
Garnett McKeen Laboratory, Inc., Islip,  New York
DNA reductase, 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 (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.
Other Scientific Research References
"Synthetic DNA Reductase" (Garnett), J. Bioinorg. Chem. V. 59, P. 231 Aug. '95, Lubeck

"Charge Relay from Molybdate Oxyradicals to Palladium Lipoic Complex to DNA" (Garnett and Garnett, Conference on Oxygen Intermediates in Nonheme Metallobiochemistry, 1996)

"Developmental Electronic Pathways and Carcinogenesis"(Garnett, Remo, and Krishnan, Sixth International Conference of Bioenergetic Medicine, 2002)

"Increased Pseudoinductance in Paired Mixtures of Biopolymers is a Model for Twin Wire Mutual Inductance in RNA and DNA"(Garnett and Remo, 198th Meeting of Electrochemical Society, Abstract 1152, Phoenix 2000)

Impedance Spectroscopy of DNA"(Garnett and Garnett, Journal of Inorganic Biochemistry, V.74, 1999)

"Mesophase Interactions Between Biological Polymers"(Garnett and Remo, 200th Meeting of Electrochemical Society, Abstract 1132, 2002)

"Pulsed Electrospinning of Biopolymers"(Garnett and Krishnan, 201st Meeting of Electrochemical Society, Abstract 78, Philadelphia 2002).

"Soluble Sensors of Telephonic Signals" (Garnett and Remo, 200th Meeting of Electrochemical Society, Abstract 185, 2000)

"Synthetic DNA Reductase"(Garnett, Journal of Inorganic Biochemistry, V.59, C48, p.231, 1995)

"Dissipative Impedance in a Doped Liquid Crystal&"(Krishnan and Garnett, 1st Spring Meeting of the International Society of Electrochemistry, Abstract P06, Spain 2003)

"Dopant Catalyzed Charge Dissipation in a Liquid Crystal" (Krishnan and Garnett, 203rd Meeting of Electrochemical Society, Abstract 2703, Paris 2003)

"Duplex semiconductor behavior of mercury electrode in aqueous solutions" (Krishnan and Garnett, 226th American Chemical Society National Meeting, Abstract Inor.0028, New York 2003)

"A New Model for DNA Charge Transfer: Variable Electronic Circuitry" (Garnett and Krishnan, 204th Meeting of Electrochemical Society, Abstract 1377, Orlando 2003)

"Modulation of Impedance in DNA Solutions by Ions and Molecules: 1. Effect of Alkali Metal Ions" (Krishnan and Garnett, 204th Meeting of Electrochemical Society, Abstract 1378, Orlando 2003)

"Peroxide Doping of DNA Enables Dissipative Impedance" (Garnett and Krishnan, 204th Meeting of Electrochemical Society, Abstract 1379, Orlando 2003)



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