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Chemical Protection Against Ionizing Radiation John C University of the Pacific Scholarly Commons School of Pharmacy and Health Sciences Faculty Thomas J. Long School of Pharmacy and Health Books and Book Chapters Sciences 8-1-1984 Chemical Protection Against Ionizing Radiation John C. Livesey University of the Pacific, [email protected] Donald J. Reed Lucile F. Adamson Follow this and additional works at: https://scholarlycommons.pacific.edu/phs-facbooks Part of the Medicine and Health Sciences Commons Recommended Citation Livesey, John C.; Reed, Donald J.; and Adamson, Lucile F., "Chemical Protection Against Ionizing Radiation" (1984). School of Pharmacy and Health Sciences Faculty Books and Book Chapters. 17. https://scholarlycommons.pacific.edu/phs-facbooks/17 This Book is brought to you for free and open access by the Thomas J. Long School of Pharmacy and Health Sciences at Scholarly Commons. It has been accepted for inclusion in School of Pharmacy and Health Sciences Faculty Books and Book Chapters by an authorized administrator of Scholarly Commons. For more information, please contact [email protected]. 1,A1 82 CEI CAL PROTECTION AGAINST ON17ING RADIATION( U OREGONSTATEUNVCORVA tS JCLVFSE ET AL AUG 84 RI 15644 £MWE 08183 0 Enh.I-EEOMOEE ItU a Mae L il L4WIla Unclassified Ser-U1111V CLASS4Fic ATION OP ?"Is PAO& M~o boo atw__________________ REPORT DOCUMENTATIOM PAGE fhSII0MCONI 4 ?l?LIt(ftWSVWI#I* S ?YP1 OF REPORT a PERIOD COVESEO Final Report Chemical Protection Against Ionizing Radiation * peps~ ORO. Of"?, u UCRL-JarVV' J. C. Livesey, D. J. Reed, L. F. Adamson P0O 1369905 * Sag.PCVRM63AugJAT?. "NAN A60194 T.t~""WK It ASK Environmental Health Sciences Center A....ww U 61M w Oregon State University Corvllis7331Work OR Unit 24320 ". COO~LLINGu OVVICE "AMe AN ADD"ES It. IMPORT OAIS Federal Emergency Management Agency August 1984 Washington, D.C. 20472 151se"O A9 I.NTOR1118 A4NC; NAWE A AMSGRE0r 40000,00 6011 ca-WOMeuOM"). IS. SECURITY CLAUS (Of Ote #"We) Lawrence Livermore National Laboratory Unclassified Approved for Public Release; Distribution Unlimited 17 ~e.eEetotmU~@ BIAEIrl.lock". 010NSII 000ea1141h0001) to SUPP&MONARY Il0715 1181 WORDS (CN*Wo do feeem ow of 00000eI', mEd1~100,r 6F 610" 01016o Chemical Radiation Protection Radiation Chemistry Radioprotectors Radiation Biology Ise Radiolysis VThe scientific literature on radiatin-protective drugs is reviewed. Eqpha i Isplaced on the mechanisms involved in determining the sensitivity of bio- logical material to Ionizing radiation and mechanism of chemical radioprotec- ties. In Section 1, the types of radiation are described and the effects of ion ising radiation on biological systsms are reviawed. The effects of ionizing radiation are briefly contrasted with the effects of non-ionizing radiatioa.n o contitvuied S~ uim s.ifiAT*PIusp 20. Abstract (continued) I- Section 11 reviews the contributions of various natural factors which Influence the inherent radiosensitivity of biological systems. Included in the list of these factors are water, oxygen, thiols, vitamins and antioxi- dants. Brief attention is given to the model describing competition between oxygen and natural radloprotective substances (principally, thiols) In deter- mining the net cellular radiosensitivity. Several theories of the mechanism(s) of action of radioprotective drugs are described in Section III. These mechanisms include the production of hypoxia, detoxication of radiochemical reactive species, stabilization of the radiobiological target and the enhancement of damage repair processes. Section IV describes the current strategies for the treatment of radiation injury. Likely areas in which fruitful research might be performed are described In Section V. Appendices are devoted to lists of currently-funded research projects Involving chemical radi aion protection and a brief compendia of compounds which have been tested t~r radioprotective activtty. ii DEPARTMENT OF BIOCHEMISTRY AMD BIOPHYSICS and ENVIRONMENTAL HEALTH SCIENCES CENTER OREGON STATE UNIVERSITY CORVALLIS, OREGON 97331 CHEMICAL PROTECTION AGAINST IONIZING RADIATION by John C. Livesey Donld Donald3.. RedsnReed AcesioAceso orAr PTTC TAB noB. if 17 tribuction- Avjailit ~~ AUGUST 1980 Speclta Prepared for FEDERA EMERGENCY NWMENENT AGENCY washirdol D.C. I kknowl dgimts We would like to acknowledge the assistance of several Individuals whose efforts contributed to the completion of this report. A number of researchers in the fields of radiation chemistry, biology and oncology shared published and unpublished information which contributed to this report. Included In this nekimp,erous groupE. Fickweiler, are: G. E. C. Adams, Koch, K.-O.L. Miles, Asmus, M. B. Paterson, H. J.Bielski, J. A. Raleigh,C. Sorek, L. J. Revesz, E. Riklis, C. A. Waldren, and H. R. Withers. A large amount of credit goes to Nanette Cardon for her Indefatigable efforts in maintaining the organization, filing and computer searching of the many bytes of information on radiation protection which we have collected during the course of this project. Her patient, diligent and efficient typing and printing of this manuscript is also gratefully appreciated. (I PrefWAe The field of radiation protection carries a certain anount of stigma from the public about the sources of radiation, Its effects, and uses. Certainly, few would fail to acknowledge the beneficial effects of diagnostic radiology and radiation therapy. However, the public concern over low levels of radiation, coupled with concern over nuclear issues in general, Is pressing and likely to continue. In this atmosphere of concern, the topic of chemical protection against ionizing radiation Is viewed by many people as a means of skirting or minimizing the hazards of exposure to Ionizing radiation, or as a way to make increased exposure more acceptable. However, radiation exposure is with us as a fact of life, and accidents with ionizing radiation sources do occur, as recent- ly happened in Juarez, Mexico (Marshall, E., Scence 1984 223, 1152-1154). The presence of nuclear power plants, and their finite Tifetime, will result in occupational exposure to radiation as they are decommissioned early in the next century. As one looks at the types of radioprotectors and their effectiveness, 4 the notion that radiation exposure will Increase because of reliance on chemical means of preventing the damage of ionizing radiation becomes quite Implausible. Certainly, no chemical means can prevent or even significantly reduce the horrors of strategic use of nuclear weaponry or the large scale accidential emission of radiation from power sources. However, benefits from effective radioprotectors can be realized. Some of the hazards of modest accidential exposure to radioactive materials (such as the recent Juarez Incident) may be *. lessened by the application of radloprotectors or effective treatments for "radiation sickness.* Individuals who are genetically highly susceptible to natural radiation sources may derive benefit from research on chemical radiopro- tection. The clinical use of radioprotective agents as prophylactic adjunct therapy in radiation oncology has been a continuing goal of radiation oncolo- gists for many years. It is for these purposes that we have reviewed the liter- ature on chemical protection against Ionizing radiation and submit this report on our efforts. ii I The scientific literature on radiation-protective drugs is reviewed. Emphasis is placed on the mechanisms Involved in determining the sensitivity of biological material to ionizing radiation and mechanisms of chemical radioprotection. In Section 1, the types of radiation are described and the effects of ionizing radiation on biological systems are reviewed. The effects of ionizing radiation are briefly contrasted with the effects of non-Ionizing radiation. Section I reviews the contributions of various natural factors which influence the inherent radiosensitivity of biological systems. Included in the list of these factors are water, oxygen, thiols, vitamins and antioxi- dants. Brief attention is given to the model describing competition between oxygen and natural radioprotective substances (principally, thiols) In deter- mining the net cellular radiosensitivity. Several theories of the mechanism(s) of action of radioprotective drugs are described In Section 111. These mechanisms include the production of hypoxia, detoxication of radiochemical reactive species, stabilization of the radiobiological target and the enhancement of damage repair processes. Section IV describes the current strategies for the treatment of radiation injury. Likely areas in which fruitful research might be performed are described in Section V. Appendices are devoted to lists of currently-funded research projects Involving chemical radiation protection and a brief compendium of compounds which have been tested for radioprotective activity. ~zi I1! TABLE OF CONTENTS 1. Effects of Radiationon iological Sytm ....... .... 1. B. Types of Ionizing Radiation....................................... 1. C. Effects of Ionizing Radiation at the Atomic and Molecular Level s. .. .. * ...** **o .. ***. **.. o .............. 1. Modes of energy transfer: ionization, excitation, 2. Significant variables: LET, dose, dose rate, tissue 3. Critical target molecules: Nuicleic acids, membrane 1ipids, and enzymes . ........................ ................... 6. 0. Effects of Ionizing Radiation at the Functional and Systemic Levelss.. ... ... *. **** ************* ... *... *. *...................... 9. 1. Cell survival curves and models of cellular inactivation.
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