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Dr. Merrill Garnett Bio | Scientific Research | View Videos


 
INTERNATIONAL SYMPOSIUM ON APPLICATIONS OF ENZYMES IN CHEMICAL AND BIOLOGICAL DEFENSE.

May 2001
Plenary Session Abstracts
DNA Reductase: A Synthetic Enzyme with Opportunistic Clinical Activity Against Radiation Sickness

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.
 

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