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Extracellular DNA as Environmental Factor

#1282


Study of Low-Molecular Extracellular DNA as a Factor of Programmed Death due to the Surrounding Medium Action

Tech Area / Field

  • MED-DID/Diagnostics & Devices/Medicine
  • MED-RAD/Radiomedicine/Medicine

Status
8 Project completed

Registration date
21.05.1998

Completion date
16.11.2004

Senior Project Manager
Pobedimskaya D D

Leading Institute
VNIIEF, Russia, N. Novgorod reg., Sarov

Supporting institutes

  • Institute of Military Medicine, Russia, St Petersburg

Collaborators

  • Korea Research Institute of Standards and Science, Korea, Taejeon\nSigma Five Associates, USA, NM, Albuquerque\nUniversité d'Orléans, France, Orleans

Project summary

Goals of the Project: Investigation of low-molecular extracellular DNA at external influence.

In the framework of the Project the following problems should be solved:


· process programming death (apoptos) cells investigation under influence of ionizing radiation and high electromagnetic fields;
· dynamics of accumulation low-molecular extracellular fraction of DNA in blood plasma for estimate value these influence and utilization these indices as biodosimetry.

Events of the Project:

1. Development of chemical and biological investigations methods of low-molecular extracellular fraction of DNA in blood plasma.

2. Realization dependence accumulation low-molecular extracellular fraction of DNA in blood from dose of irradiation and intensity of magnetic and electric fields.

3. Development theoretical bases formation of low-molecular extracellular fraction of DNA in extreme conditions.

4. Investigation structure of low-molecular extracellular fraction of DNA (nucleotid structure).

5. Delivery recommendation about possibility utilization low-molecular extracellular fraction of DNA:


— as biodosimeter;
— as valuation of effectiveness pharmacological preparation and e.t.

Execution investigations in this project resulted in essential improvement understanding of nature formation low-molecular extracellular fraction of DNA in extreme conditions. Modification low-molecular extracellular fraction of DNA in blood may be used as biodosimeter in evaluation and control of surrounding and in the future may open the way and methods of pharmacological correction appeared violations in organism.

Technical Approach and Methodology:

The main part of the experiments will be performed on white rats, which will be purchased in Moscow nursery in lots of 30-50 rats. After transportation there will be 30 days quarantine in the own vivarium in the standard diet. Animals with the mass of 180-220 g will be used at the experiments. After the testing and blood selection some analysis will be performed in VNIIEF, and part of the tests will be preserved and sent to SRI of Military Medicine. At long radiation effect blood will be taken after definite time intervals.

Radiation investigations will be performed at radiation doses from 1 to 100 Gr. Electron accelerator with the electron beam energy in the pulse 4 MeV and current 30 kA will be used for pulsed irradiation. X-ray radiation dose for one pulse will be 10 r/m. Static investigations will be carried out on the IGUR-1 device (gamma-radiation 137Cs) with the dose intense 1.9 Gr/min. Others RFNC-VNIIEF devices will be used of necessity.

Influence of magnetic fields will be studied on three devices: constant magnetic field up to 3 T, pulsed magnetic field up to 50 T and ultra-high magnetic field up to 1000 T. Blood plasma will be studied at ultra-high magnetic fields. More low fields will be used at the experiments with animals.

Electrical effects will be studied in strip lines, where the field could be of several kW/m. Special interest represent investigations in irrotational pulsed field. Electromagnetic effect will be realized in narrow frequency band in resonators and in wide frequency range by the direct irradiation.

Chemico-analytical methods, including spectrophotometry, ionometry, liquid chromatography, element analysis, will be used for blood analysis. Separation of low-molecular DNA fraction from the blood plasma and pision into high-polymeric and low-polymeric DNA fractions will be realized with electrophoresis and quantitatively determined by the methods of spectrometry.

Low-molecular DNA fraction structure (nucleotide structure) will be determined by secretation with further application of International database of genome analysis. Evaluation of pharmacological preparations will be made on the criterion of low-molecular DNA fraction accumulation.


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