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Adaptation of Mammals to Irradiation

#3665


Adaptation of Mammalian Organism to Irradiation: Modeling Approach

Tech Area / Field

  • BIO-RAD/Radiobiology/Biotechnology
  • ENV-MRA/Modelling and Risk Assessment/Environment

Status
3 Approved without Funding

Registration date
12.12.2006

Leading Institute
Research and Technical Center of Radiation-Chemical Safety and Hygiene, Russia, Moscow

Supporting institutes

  • VNIIEF, Russia, N. Novgorod reg., Sarov

Collaborators

  • University of Alberta / Faculty of Science, Canada, AB, Edmonton\nKyoto University / Research Reactor Institute, Japan, Osaka\nNASA / Ames Research Center, USA, CA, Moffett Field\nUniversity College of Dublin / School of Medicine and Medical Science, Ireland, Dublin\nNASA / Lyndon B. Johnson Space Center, National Aeronautics and Space Administration, USA, TX, Houston\n[Individual specialist]\nUniversity of Florida / Department of Mathematics, USA, FL, Gainesville\nMcMaster University, Canada, ON, Hamilton\nOsaka Prefecture University, Japan, Osaka\nUniversidad de Alcala, Spain, Madrid

Project summary

The Project is a fundamental research in the field of radiation biology and ecology and in the field of mathematical modeling of radiobiological effects. The Project goal is modeling investigations of the adaptation of a mammalian organism to radiation. This effect, known as a radioadaptive response or acquired radioresistance, is under active study in the present-day radiobiology. The radioadaptive response is induced in mammals by both single and chronic low-level preirradiation and manifested in lowered mammalian mortality after challenge exposures to sub-lethal or lethal doses. The reasons of the mammal death at two above-indicated regimes of challenge irradiation are damages of two vital (critical) body systems (hematopoiesis and small intestine, respectively). With regard for these experimental facts, to study the radioadaptation mechanisms, mathematical models will be developed, which describe the effects of priming and challenge irradiation on these critical body systems in mammals (mice). Modeling results on the dynamics of hematopoietic and small intestine epithelium systems under exposures in question will be juxtaposed with pertinent experimental data, available in the literature, on survival of mammals (mice) in order to find the reason-consequences relationships between the radiosensitivity modifications induced by preirradiation in these systems and in the organism as a whole. On this basis, the radioadaptation mechanisms will be elucidated and the key parameters will be determined which can be used as indicators of the acquired radioresistance for the hematopoietic and small intestine epithelium systems and for the organism as a whole. In the course of modeling studies, the "optimal" regimes of priming and challenge exposures will be found under which the radioprotection effect of priming irradiation on mice is maximum. Undoubtedly, the use of these results in planning new purposeful experiments can reduce the number of preirradiation schemes that will lead to economical benefits and will speed up respective experimental studies.

The project investigations are important for the fundamental science because they promote the development of the systems and quantitative approaches in radiation biology. They will allow one to reveal the mechanisms of the radioadaptive response which has no any conventional interpretation yet. Without doubts, determining the indicators of the acquired radioresistance for hematopoietic and small intestine epithelium systems and for the mammalian organism as a whole is of a special theoretical and practical interest. These results will be helpful for specialists in the radiation ecology, space biology, and medical radiology when solving the problems connected with the effects of fractional irradiation. Besides, after appropriate identification, the mathematical models of two critical body systems, that will be developed in the framework of the Project, can form a basis of mathematical tools intended for the estimation of the risks of fractional irradiation for humans.

The foundation for successful implementation of the project is high competence and experience of the project manager, Smirnova O.A., in the field of mathematical modeling of radiation effects on vital body systems in mammals and in the field of radiation risk assessment. Smirnova O.A. is a Doctor of Science in Physics and Mathematics since 1992. Her scientific results are well-known in the international scientific community. They have been reported and discussed at 41 International Conferences and published in leading international scientific journals (Mathematical Biosciences, Health Physics, Acta Astronautica, Simulation Modeling Practice and Theory, Physics of Particles and Nuclei, Folia Microbiologica). Smirnova O.A. is the author of 132 publications including 2 monographs. She is a member of Scientific Commission F (Life Sciences as Related to Space) of Committee on Space Research (COSPAR).

The pledge of success of the project implementation is also high expertise of the rest 6 members of the project team, 4 members among them being weapon specialists. Zvonov F.A., Kovalenko O.V., Sukhikh A.S. are the senior scientific researchers with great experience in frame of physical processes modelling. Kuznetsov A.M. and Baryshnikova O.V., engineers, are characterized by high professionalism. Darenskaya N.G., Professor, Doctor of Science in Medicine, is a great authority in the field of radiation biology and medicine. She is the author of more than 300 publications including 9 monographs. Professor Darenskaya N.G. is a State prize winner (1986).

The Project meets goals and objectives of the ISTC. Implementation of the Project will enable weapon scientists to redirect their research activity to peaceful areas. In the framework of the project they will be integrated into the international scientific community due to the interchange of information with abroad collaborators. In addition, the realization of the Project will support fundamental research for peaceful purposes, namely, in the field of radiation biology and ecology and in the field of mathematical modeling of radiobiological effects and radiation risk assessment.

The most representative publications of the project manager:

  1. Smirnova O.A. Radiation and organism of mammals: Modeling approach (monograph). Scientific-Publishing Centre “Regular and Chaotic Dynamics”, Institute of Computer Science, Moscow- Izhevsk, 2006, 224 p. (Russian).
  2. Kovalev E.E., Smirnova O.A. Estimation of radiation risk based on the concept of inpidual variability of radiosensitivity. AFRRI Contract Report 96-1. Defense Nuclear Agency Contract DNA001-93-C-0152. Bethesda, Maryland, USA: Armed Forces Radiobiology Research Institute, NWED QAXM, 1996, 203 p.
  3. Stepanova N.V., Petrova T.A., Smirnova O.A Dynamical models of cell populations (monograph). 1992, Dep. in VINITI N 239-V92, 23.01.92, two volumes, 421 p. (Russian).
  4. Smirnova O.A. Mathematical modelling the radiation effects on humoral immunity. Advances in Space Research, 2006, v. 37, p. 1813-1822.
  5. Smirnova O.A., Yonezawa M. Radioresistance in mammals induced by low-level chronic irradiation: modeling and experimental investigations. Health Physics, 2004, v. 87 (4), p. 366-374.
  6. Smirnova O.A. Simulation of mortality dynamics for populations of mammals (mice) exposed to radiation. Simulation Modelling Practice and Theory: Advances in modelling and simulation in biology and medicine. Edited by Y. Hamam and F. Rocaries, 2004, V. 12, No 2, p. 171-182.
  7. Smirnova O.A. Comparative risk assessment for homogeneous and nonhomogeneous mammalian populations exposed to low level radiation. In: I. Linkov and A.B. Ramadan (eds.) Comparative Risk Assessment and Environmental Decision Making. NATO Science Series. IV. Earth and Environmental Sciences - Vol. 38. Dordrecht, The Netherlands: Kluwer Academic Publishers, 2004, p. 385-392.
  8. Shatkin J.A., Andreas I., Apul D.S., Attia A., Brambilla M., Carini F., Elshaeb Y., Girgin S., Gitis I., Mandarasz T., Small M., Smirnova O., Sorvary J., Tal A. A proposed framework for multinational comparative risk analysis: pesticide use, impacts and management. In: I. Linkov and A.B. Ramadan (eds.) Comparative Risk Assessment and Environmental Decision Making. NATO Science Series. IV. Earth and Environmental Sciences - Vol. 38. Dordrecht, The Netherlands: Kluwer Academic Publishers, 2004, p. 149-168.
  9. Smirnova O.A., Yonezawa M. Radioprotection effect of low level preirradiation on mammals: modeling and experimental investigations. Health Physics, 2003, v. 85(2), p. 150-158.
  10. Sakovich V.A., Smirnova O.A. Modeling radiation effects on life span of mammals. Physics Particles and Nuclei, 2003, v. 34, No.6, p. 743-766.
  11. Smirnova O.A. Mathematical modeling of radiation-induced autoimmunity. In: Mathematical Modelling & Computing in Biology and Medicine. 5th ECMTB Conference 2002. Editor: V. Capasso. Milan: Milan Research Centre for Industrial and Applied Mathematics, 2003, p. 392-402.
  12. Smirnova O.A. Mathematical model for assessment of radiation risk on long space mission. Advances in Space Research, 2002, v. 30, No 4, p. 1005-1010.
  13. Smirnova O.A. Mathematical modeling of mortality dynamics of mammalian population exposed to radiation. Mathematical Biosciences, 2000, v. 167, p. 19-30.
  14. Smirnova O.A. Mathematical models of hematopoiesis dynamics in nonirradiated and irradiated mammals. BioMedSim'99. 1st Conference on Modelling and Simulation in Biology, Medicine and Biomedical Engineering, Noisy-le-Grand, France, 20-22 April 1999. Proceedings. Paris: Groupe ESIEE, 1999, p. 105-109.
  15. Smirnova O.A. Mathematical modeling of the effect of ionizing radiation on the immune system of mammals. Physics of Particles and Nuclei, 1996, v. 27, No 1, p. 100-120.
  16. Kovalev E.E., Smirnova O.A. Life-span of irradiated mammals. Mathematical modelling. Acta Astronautica, 1994, v. 32, 649-652.
  17. Zukhbaya T.M., Smirnova O.A. An experimental and mathematical analysis of lymphopoiesis dynamics under continuous irradiation. Health Physics, 1991, v. 61, p. 87-95.
  18. Levi M.I., Smirnova O.A. Cyclic kinetics and mathematical expression of the primary immune response to soluble antigen: VII. The conveyer hypothesis and its mathematical expression. Folia Microbiologica, 1977, v. 22, p. 117-127.


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