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Abstract from Grachev SA, Sverdlov AG. Chemical Protection Against X-Ray, Gamma, and Neutron Radiation

Experiments in mice showed that intraperitoneal (i.p.) injection of unithiol (sodium salt of 2,3-dimercapto-l-propanesulfonic acid) diminished toxicity of several aminothiol radioprotectors, increasing the LD50 of cystamine by 40% and aminoethanisothiuronium bromide hydrobromide (AET) by 64%. The optimum ratio for the doses is 0.5 molar equivalent of unithiol per radioprotective thiol. A new radioprotector (mixed disulfide of cysteamine and unithiol—MDCU) has a weak toxicity: the LD50 is 750 mg/kg i.p. The use of unithiol makes it possible to increase the dose of the SH-radioprotectors, enhancing the dose reduction factor (DRF) of cystamine and AET by 30% for x-ray irradiation. A somewhat lesser effect is observed with fission neutron irradiation. The DRF of MDCU is equal to 1.6 for x-ray irradiation and is 1.1 for neutron irradiation. The mechanism of antitoxic action of unithiol could not be detected in Chinese hamster fibroblasts. It may be caused by the competition of unithiol and the SH-radioprotectors for certain, as yet undetermined, biochemical structures in brain neurons. It is also possible that unithiol may decrease penetration of SH-radioprotectors into the brain.

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Preface from Grachev SA, Sverdlov AG. Chemical Protection Against X-Ray, Gamma, and Neutron Radiation

One of the major long-term research goals of the Armed Forces Radiobiology Research Institute (AFRRI) has been the study and development of agents, either singly or in combination, that would protect personnel exposed to either photon or neutron radiation, or both. There are several scenarios, besides the obvious one of a nuclear weapon(s) detonation, where military personnel could be subjected to a single or mixed radiation field; they include cleanup operations after a reactor accident, such as that at Chernobyl, or a weapons accident or incident.

Criteria for a preventive regimen should include (1) significant dose modification factor (dose reduction factor, or DRF); (2) minimal if any side effects and no long-term toxicity; (3) oral administration, preferably no more than once daily; and (4) minimal reduction in effectiveness when administered soon after exposure rather than prior to exposure.

Some of the most effective agents to date have been aminothiols and their derivatives. Unfortunately, most of these agents have side effects such as nausea, vomiting, hypotension, weakness, and fatiguability that, while not precluding their use in clinical radiation therapy, have rendered them unsuitable for a military operations scenario. Researchers at AFRRI (Weiss et al. 1993; Landauer et al. 1993) demonstrated that administration of caffeine mitigated the neurotoxicity caused by administration of WR-3689 and WR-2721, though other authors have found that caffeine in higher doses aggravated these symptoms. Clearly, the need for a radioprotector that is both effective and safe still exists.

Dr. Joseph F. Weiss visited, on behalf of AFRRI, the authors of the present report in their laboratory at Gatchina, Russia. He was impressed by the work they were doing in this field and how it supplemented AFRRI's research along different lines toward this same goal. Their approach, spelled out in the section “Introduction,” will not be repeated here.

Briefly, the authors used a nontoxic thiol compound to block the biochemical receptors in cells of the target tissues for the side effects while not simultaneously lowering the DRF. They also tested a new compound that they synthesized for efficacy and toxicity protection. These combinations were tested against both neutron and photon irradiation using a mouse model. The authors recommended that these successful preparations be used in a large animal (canine) model, and, if successful, be followed by human toxicity studies. Realizing that the parenteral routes of administration used in their study are unsuitable for a field situation, they also outlined steps for development of oral regimens.

While this document does not reflect the opinion of AFRRI or the Department of Defense regarding the suitability of the described regimens in an operational situation, it does present a thought-provoking step toward the development of an effective yet nontoxic means of radiation protection and may stimulate further research along these or perhaps slightly different lines.

Grateful acknowledgment is given to the following scientists at AFRRI whose advice and constructive criticism were of immense value in the editing of this manuscript: Drs. E. John Ainsworth, Ramesh Bhatt, K. Sree Kumar, and Terry Pellmar and Mr. Henry Gerstenberg. Any errors in editing, however, are entirely my responsibility.

Glen I. Reeves, M.D.
NIS Initiatives Coordinator
Armed Forces Radiobiology Research Institute

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Abstract from Chumak VV, Likhtarev IA, Sholom SS, Pasalskaya LF, and Pavlenko HV. Retrospective Reconstruction of Radiation Doses of Chernobyl Liquidators by Electron Paramagnetic Resonance

Accurate, reliable dose reconstruction is a critical component in the epidemiological followup of liquidators. Dosimetry of teeth by electron paramagnetic resonance (EPR) is a state-of-the-art laboratory technique that is key to this effort. The Scientific Center of Radiation Medicine (SCRM) has developed and refined this technique in order to meet the practical demands of large-scale epidemiologic followup of the Chernobyl liquidators. Independent analysis using similar technology was performed by investigators at the University of Utah and showed good correlation with the SCRM results. The lower limit of detection for reliable dose reconstruction was 100 mGy. Techniques were applied to samples from approximately 135 liquidators involved in cleanup activities within the first 2 years after the Chernobyl accident in 1986. Mean dose was 287 mGy, geometric mean was 205 mGy, and median dose value was 200 mGy. The reconstructed dose values range from 30 to 2220 mGy. Correlation of results between the two institutions was generally within 17%. This report also addresses some confounding factors (previous medical x-ray exposures, ultraviolet light effects on anterior teeth, nonlinearity of dose response curves below 100 mGy) and how to deal with them.

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Description of Dubois A, King GL, Livengood DR (eds) (1995) Radiation and the Gastrointestinal Tract

The publisher of the book Radiation and the Gastrointestinal Tract called it "a true technology transfer among scientists working in government, academia, and the pharmaceutical industry" and notes that "chapters [are] written by a unique blend of basic scientists and clinicians."

The book evolved from a September 1993 international symposium sponsored jointly by the U.S. Department of Defense's Armed Forces Radiobiology Research Institute (AFRRI) and Uniformed Services University of the Health Sciences (USUHS). The symposium was supported in part by grants from the Pennsylvania firm U.S. Bioscience as well as the British firms SmithKline Beecham Pharmaceuticals and Rorer Rhone Poulenc.

In the foreword, the editors describe the field of study as "particularly important because of growing medical needs and because of the documented occurrence of [radiation] accidents involving overexposure of healthy subjects and/or patients." A unique relationship exists between basic scientists and clinicians in this field because, according to the editors, "answers to some of the clinically relevant questions posed by such scenarios have been reached through cellular and animal research, and the results obtained lead to hypotheses that have been tested through clinical protocols."

Contributors represent 12 U.S. and British organizations that include, in addition to the sponsors and supporters, Glaxo Research Institute, North Carolina; Massachusetts General Hospital, Massachusetts; Spellman College, Georgia; Hines Veterans Administration Medical Center, Illinois; Lehigh Valley Hospital Center, Pennsylvania; Medical College of Wisconsin, Wisconsin; University of Iowa College of Medicine, Iowa; and The Queen's University of Belfast, United Kingdom.

The authors in each of 38 articles describe their most recent data, present a consensus, and discuss what investigations are still needed. The coeditors are Andre Dubois, MD, PhD, of the Uniformed Services University of the Health Sciences (USUHS) and Gregory L. King, PhD, and David R. Livengood, PhD, both of the Armed Forces Radiobiology Research Institute (AFRRI). Both organizations are in Bethesda, Maryland.

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