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Genetic Health Prognosis

#1286.2


Integrated Genetic Health Prediction for People Exposed to Hazardous Environments: A Method Based on Genotype and Radiosensitivity Analysis

Tech Area / Field

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

Status
8 Project completed

Registration date
10.07.2000

Completion date
18.07.2006

Senior Project Manager
Rudneva V Ya

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

Supporting institutes

  • Institute of Theoretical and Experimental Biophysics, Russia, Moscow reg., Puschino\nInstitute of General Genetics, Russia, Moscow

Collaborators

  • Humboldt Universität / Institute of Human Genetics, Charite - Humboldt University zu Berlin, Germany, Berlin\nDepartment of Genetics, the University of Leicester, UK, UK, Leicester\nUniversity of California / Division of Environmental Health Sciences, USA, CA, Washington\nInstitute of Medical Radiobiology, Essen, Germany, Germany, Essen\nLawrence Livermore National Laboratory, USA, CA, Livermore

Project summary

The objective of PDG # 1286 is to:
· look for foreign collaborators and investigate possibilities of joint genetic research with discussion of new promising methods;
· develop and coordinate the Work Plan with collaborators;
· develop information on the project subject for presentation to international scientific meetings and publication in scientific periodicals.

Initial experiments to test genetic study methods.

Micronuclear test to study low-dose effects of genetically toxic environments (ITEB RAS).

Initial study was carried out to investigate applicability of micronuclear test for the low-dose effects of various genotoxic environments on flora and fauna entities in vitro and in vivo. Slightly modified, standard procedures were used to make and tint preparations to measure the fraction of micronuclear (MN) cells for different test entities. These experiments obtained MN cell occurrence rate vs. dose for Vicia faba sprouts, fibroplast cultures of Chinese hamster and human peripheral lymphocytes, and bone marrow cells of mice when they were exposed to - radiation (5 to 50 cGy) and chemical mutagens at a low dose. These dose- dependence curves show complex non-linear behavior, which led us to conclude it unreasonable to extend the chromosome damage of cells in high-dose range to low-dose case. The experimental data proved the high sensitivity and versatility of micronuclear test in the genome study of cell exposed to low-dose unfriendly environments.

PCR amplification of DNA microsatellite loci - a method to identify genotype (IGG RAS).

The PCR amplification of DNA microsatellite loci was tested for applicability in genotype identification further under Project #1286. The project participants of Vavilov IGG RAS did that as part of PDG #1286 jointly with the Department of Genetics, University of Leicester, UK. For this purpose, blood samples had been taken from 102 healthy male donors, Russians, 20 to 50 of age. The IGG scientists had DNA preparations extracted from these samples using reactants with guanidinethiocyanate as denaturant. The ready DNA preparations were taken to the Department of Genetics, where they were tested to identify suitable DNA microsatellite markers on Y- chromosome that would be easy to use in research under Project #1286. This activity was carried out jointly by the Russian and British scientists.

Study of congenital anomalies in children of the population located near a nuclear facility (RFNC-VNIIEF).

Examination of indications of the physical development and health status with children and grandchildren of the people who either work in radiologically unfavorable environments at nuclear weapons facilities or live in the adjacent areas, is a challenge to radiation medicine and epidemiology

Congenital anomaly rate was assumed to indicate the physical development and health status in children as one among the most informative.

Eight thousand newborns of the Sarov population in 1968-1974 were examined for congenital anomalies. The rate of congenital anomalies was found for these newborns and how they are distributed by the body parts. The rate of anomalies such as congenital hip dislocation, gastrointestinal atresias or hemangiomas was observed to be credibly higher than the reported by foreign authors. Also, the number of children with congenital anomalies for the cohort of parents who lived long time in the city was found to be credibly more than that for the cohort of parents who had stayed one to three years in the city. The point under discussion is cause- effect relations of the congenital anomalies in children and different environments, including radiation.

Computational and experimental developments for irradiation of blood samples.

The following was accomplished within the Development Grant:


· implemented a setup for blood irradiation;
· investigated operation options of the X-ray irradiator of blood samples for inpidual radiosensitivity analysis;
· performed calculation of the absorbed dose distribution in the air near the accelerator tube exit window;
· performed absorbed dose measurements in tissue-equivalent phantoms using TLD technique.

Publications

1. Korzeneva I.B., Styazhkina T.V., Zaichkina S.I., Elyash S.L. Possible Approach to Integrated Genetic Health Prediction for People Exposed to Hazardous Environments: A Method Based on Genotype and Radiosensitivity Analysis. Abstracts supplement for poster session: Work in Progress. 11th International Congress of Radiation Research ICRR’99, July 18-23, 1999, Dublin, Ireland.

2. Korzeneva I.B., Styazhkina T.V., Dubrova Yu. E., Malinina T.V., Prokhorovskaya V.D., Kholod O.N. Investigation of the Factors, Disguising the Radiation Effects on Human Body. Abstracts supplement for poster session: Work in Progress. 11th International Congress of Radiation Research ICRR’99, July 18-23, 1999, Dublin, Ireland.

3. Elyash S.L., Kalinovskaya N.I. Compact X-ray Irradiator on the Base of Pulsed Accelerator ARSA in Medicine and Biology. Abstracts supplement for poster session: Work in Progress. 11th International Congress of Radiation Research ICRR’99, July 18-23, 1999, Dublin, Ireland.

4. Klokov D.Yu., Zaichkina S.I., Rozanova O.M., Aptikaeva G.F., Akhmadieva A.K., Smirnova E.N., Balakin V.Yu. The adaptive response in the bone marrow cells of mice to -irradiation in vivo varied in dose. Abstracts of the 11th International Congress of Radiation Research ICRR’99, July 18-23, 1999, Dublin, Ireland, p. 255.

5. Elyash S., Avilov E., Korolov V., Yur’ev A. ERINA-350 small-size high-power short-pulse generator for health and biology applications. Abstracts of the 2nd International Conference “Problems of Electromagnetic Safety of the Human Being. Fundamental and Applied Research”, September 20-24, 1999, Moscow, p. 186.

6. Elyash S. L., Kalinovskaya N.I., Karpenko I.I. ARSA small-size pulse accelerator for applications in medicine and biology. Abstracts of the 2nd International Conference “Problems of Electromagnetic Safety of the Human Being. Fundamental and Applied Research”, September 20-24, 1999, Moscow, p. 151.

7. Elyash S.L., Kalinovskaya N.I. Small-size X-ray irradiator based on ARSA accelerator for biomedical applications. Abstracts of the VII International Ecological Symposium “Ural atomic. Ural industrial. Ural science to address environmental problems”, September 28-30, 1999, Ekaterinburg, p. 185.

8. Elyash S.L., Korzeneva I.B., Styazhkina T.V. Possible approach to integrated genetic health prediction for people exposed to hazardous environments. Abstracts of the VII International Ecological Symposium ”Ural atomic. Ural industrial. Ural Science to address environmental problems”, September 28-30, 1999, Ekaterinburg, p. 73.

9. Zaichkina S., Kondakova N. V., Rozanova O.M., et al. Protective effects of dehydroquercetin polyphenol compaund with in vivo -irradiation of mice. Abstracts of the VII International Ecological Symposium ”Ural atomic. Ural industrial. Ural Science to address environmental problems”, September 28-30, 1999, Ekaterinburg, p. 71.

10. Styazhkina T.V., Korzeneva I.B. Inborn anomalies in the posterity of people that populate areas to nuclear weapon-related facilities. Abstracts of the International Symposium “Chronic Radiation Exposure: Biological Indication Capabilities”, March 14-16, 2000, Chelyabinsk, p. 67.

11. S.I. Zaichkina, D.Yu. Klokov, 0.M. Rozanova et al The magnitude of cytogenetic adaptive response in the marrow cells of rats versus chronic gamma exposure in vivo. Published in journal “Radiatsionnaya Biologia. Radioekologia”, 1999, 39(4), pp. 404-405.

12. S.I. Zaichkina, D.Yu. Klokov, 0.M. Rozanova et al The duration of radiation adaptive response in the marrow cells of mice versus gamma exposure dose in vivo. Published in journal “Genetika”, 1999, 35(9), pp. 1274-1279.

The following papers are available for presentation to international conferences:

1. Elyash S.L., Kalinovskaya N.I. Compact X-ray irradiator on the base of pulsed ARSA accelerator in medicine and biology 30th Annual Meeting of the European Society for Radiation Biology, August 27-31, 2000, Warsaw, Poland.

2. Klokov D.Yu., Zaichkina S.I., Rozanova O.M., Aptikaeva G.F., Akhmadieva A.K., Smirnova E.N., Balakin V.Yu. The effect of low-dose acute g-irradiation on high-dose radiation-induced and spontaneous level of cytogenetic damage throughout life of mice. 30th Annual Meeting of the European Society for Radiation Biology, August 27-31, 2000, Warsaw, Poland.

3. Rozanova O.M., Zaichkina S.I., Klokov D.Yu., Aptikaeva G.F., Akhmadieva A.K., Response induced by chronic -irradiation in murine bone marrow. 30th Annual Meeting of the European Society for Radiation Biology, August 27-31, 2000, Warsaw, Poland.

4. Balakin V.Yu, Zaichkina S.I., Rozanova O.M., Klokov D.Yu., Aptikaeva G.F., Akhmadieva A.K., Smirnova E.N. Genomic stability induced by single low-dose gamma-irradiation: a new approach to the problem of lifetime prolongation. 2nd European Congress on Biogerontology. From the molecule to human. August 25-28, 2000, St. Petersburg, Russia.

5. Zaichkina S.I., Aptikaeva G.F., Rozanova O.M., Akhmadieva A.K., Klokov D.Yu., Smirnova E.N. Specific action of low doses of ionizing radiation on mammalians and plants: enhanced sensitivity and adaptive response. International Ecological Congress “Innovative Developments in Ecology and Safe Active Life Studies”, June 14-16, 2000, St. Petersburg, Russia.

6. Zaichkina S.I., Aptikaeva G.F., Rozanova O.M., Akhmadieva A.K., Klokov D.Yu., Surkenova G.N., Kuzin A. M. Combined effects of secondary biogenic and acute gamma radiation on the induction of cytogenetic damage in the bone marrow of mice in vivo. II International Congress “Low and Ultralow Fields and Radiation in Biology and Medicine”, July 4-7, 2000, St. Petersburg, Russia.

7. Zaichkina S.I., Aptikaeva G.F., Rozanova O.M., Akhmadieva A.K., Klokov D.Yu. Low-dose gamma effects on the induced and spontaneus cytogenetic damage in the lifetime of mice. International Conference “Radiation Genetics Problems at the Turn of the Century”, November 20-24, 2000, Moscow, Russia.

8. D.Yu. Klokov, S.I. Zaichkina, O.M. Rozanova, G.F. Aptikaeva, A.Kh. Akhmadieva, E.N. Smirnova, G.N. Surkenova, A.M. Kuzin In VIVO study of the adaptive response induced by radiation of different types. VIII International Symposium on Radiation Physics, June 5-9, 2000, Prague, Czech Republic.

9. O.M. Rozanova, S.I. Zaichkina, G.F. Aptikaeva, A.K. Akhmadieva, D.Yu. Klokov Combined action of cadmium (II) and lead (II) and chronic -radiation on radiosensitivity of rat bone marrow cells. VIII International Symposium on Radiation Physics, June 5-9, 2000, Prague, Czech Republic.


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