Environmental and Health Monitoring of Rehabilitate Activities
Technology of Environment and Health Monitoring of Rehabilitate Activities on the Territories of Liquidation of Land-Based Silo-Launched Battle Missiles in the Central Part of Russian Federation
Tech Area / Field
- ENV-EHS/Environmental Health and Safety/Environment
- ENV-RED/Remediation and Decontamination/Environment
3 Approved without Funding
Medical Radiological Scientific Center, Russia, Kaluga reg., Obninsk
- Scientific & Production Association “Typhoon”, Russia, Kaluga reg., Obninsk\nClosed Joint-Stock Company "Industrial Conversion Technologies", Russia, Moscow
- National Radiological Protection Board, UK, Chilton\nUniversity of Bradford, UK, Bradford\nIstituto Nazionale per la Ricerca sul Cancro, Italy, Genova\nUniversity of Texas / Medical Branch / Department of Preventive Medicine and Community Health, USA, TX, Galveston\nNational Institute of Radiological Science / Research Center for Radiation Safety, Japan, Chiba
Project summaryThe increasing mutagenic and genotoxic stress to human populations, which is mainly from environmental agents, requires accurate assessment of how the associated health risk relates to markers of genetic and environmental risk factors. Although environmental exposure is inherently low, it is prolonged and therefore carries unavoidable risks of inducing detrimental changes in the human genome. The health effect of most concern to exposed populations is the risk of inducing cancer. Thus, a reliable assay for monitoring human groups and populations exposed to mutagenic agents should be an appropriate tool for the task of elimination of excessive environmental risk factors.
Unfortunately, from the scientific point of view, the problem of accurate assessment of the risk associated with low level radioactivity and/or chemical exposure is far from being resolved. The main reason is the uncertainty associated with the necessity to extrapolate the biological response from high doses and dose rates to the conditions of environmental exposure. To be valid, such extrapolation requires a detailed understanding of the mechanisms of induced cancer and genetic disorders. In particular, at low level exposure, heterogeneity in inpidual human sensitivity can play an important role. At the genetic level this depends on inpidual polymorphisms in DNA repair capacity and can lead to significant differences in susceptibility to environmental genotoxins. Another aspect is that carcinogenesis is a multi-stage and prolonged process which is linked to both genetic and environmental risk factors.
One of the well-established precursors of carcinogenic processes is an instability in the human genome which needs to be considered in the context of the development and validation of biomarkers that link environmental exposures to human disease. Such biomarkers of genetic abnormalities can be indicative of early stages of malignancy and should be taken as an alert for enhanced medical inspection and effective treatment. Since 1992 the phenomenon of genomic instability has been demonstrated to exist both in vitro and in vivo, but the underlying mechanisms are far from clear. Moreover, the laboratory tests for direct investigation of genomic instability are rather complicated, time-consuming and still not appropriate for the monitoring of environmental risk factors.
In the proposed Project a novel environment and health monitoring technique is described based on complex molecular-genetic indices of human somatic cells. To estimate the state of an inpidual's genome we propose to use frequencies of gene mutations and chromosomal aberrations in human blood cells, as well as an inpidual immunological index of donor blood.
The fundamental scientific basis of the proposed monitoring technique is as follows:
The main long-term negative consequence of environmental low level exposure is an enhanced risk of cancer. The key point in the process of oncogenic transformation is attributed to the increasing levels of various mutations in somatic cells.
It has been shown that enhanced levels of gene mutations and chromosomal aberrations are found in patients with different types of cancer, i.e. people who developed cancers often have specific genetic disorders. The evaluated data have been collected in the International Catalogue of Chromosome Aberration in Cancer which contains information on more than 30,000 such cases. In particular, it is well known that specific translocations are early predictors of cancer and genetic disorders. For instance, the enhanced level of translocations was detected in thyroid tissue of children who were exposed to radioiodine from the Chernobyl accident and who developed thyroid tumors.
The core idea proposed in the Project is a multi-stage monitoring technique. This involves analysis of gene mutations and chromosomal aberrations in human blood cells accompanied by an estimation of the cellular and humoral immunological status of donor blood. These assays are supplemented by ecological monitoring of the environment with emphasis on radioactive and chemical contaminants. Instead of searching for the specific cancer gene mutation or chromosomal abnormality the complex estimation of the inpidual human genome capability is proposed. The analysis of blood samples will consist of the following three stages.
The first stage will involve conventional metaphase analysis of unstable chromosomal aberrations in human lymphocytes. This 1st stage will identify the subjects with frequencies of aberrations significantly above the spontaneous level and by implication likely to carry additional gene loci mutations that will be addressed in stage 2.
The second stage will be a FISH analysis by selectively painting three pairs of human chromosomes and glycophorin A (GPA) and TCR loci mutation assays. The subjects with elevated frequencies of stable aberrations (translocations) and gene mutations will be identified as an at-risk subgroup after this stage of investigation. Another important result of FISH analysis will be revealing the subjects with sub-clonal aberrations. It has been shown in both hematological disorders and solid tumors that a cytogenetically abnormal clone may be a poor prognostic sign. Unfortunately the efficiency of clone detection by 3-chromosomal FISH analysis is less than 100% but cumulative data including conventional aberrations, gene mutation and FISH results will certainly increase the detection accuracy.
The third, final stage is a precise analysis of all cases exhibiting clonal aberrations as well as other suspicious cases by extra G-band full karyotyping which is the most accurate but the most time-consuming. However, the number of such cases after the first and second stages is expected to be less than 10% of the total samples collected for monitoring. This is an acceptable number which will not preclude use of the time-consuming G-banding method. The multi-stage selective technique outlined above will be accompanied by cellular and humoral immunological analysis of donor blood. Thus, it is expected that any clear or suspicious genome abnormality of blood cells will be detected by applying this selective multi-stage technique composed of simultaneous chromosomal, gene mutation and immunological assays.
Particular pathways of environmental exposure play a very important role for monitoring. True environmental conditions of the study subjects need to be known. Therefore, the testing of environmental samples will be carried out to estimate radioactive and chemical contamination in the neighbouring terrain and/or working places of subjects.
The proposed novel monitoring technique will be applied first to an important task for the former Soviet Union regions, namely the liquidation of weapons of mass destruction (WMD). The decommissioning of WMD, in particular land-based silo-launched battle missiles, must be accompanied by a robust and effective system of complex monitoring of the environment and health conditions of the military personnel and civilian population living in the neighbouring terrain. The currently routinely used monitoring technique is based on the measurements of contaminant concentrations in various components of the environment and food chain. Unfortunately, such techniques actually do not take into account important aspects of the problem such as inpiduals' variation in susceptibility, cumulative and synergistic effects of genotoxic agents and metamorphosis of pollution in the environment. Instead of just routine monitoring, in the proposed Project the novel approach is based on a concurrent investigation of pollution of the environment and molecular-genetic indices of blood cells of the military personnel and the civilians living in the neighbouring terrain.
Specifically, this approach will be first used for evaluating the rehabilitation activities in the vicinity of silos containing intercontinental liquid-propellant ballistic missiles in the central part of the Russian Federation. Their operation, in principle, could lead to extra chemical and/or radioactive environmental contamination. In addition the explosion techniques which have been used for destroying the missiles have the potential to spread chemical and radioactive contamination of the environment and to adversely affect the health of the military and civilian populations.
The ecological monitoring of the environment for radioactive and chemical contaminants will be carried out by a laboratory analysis of samples of soil, water from the open reservoirs, drinking water, grass, air and base deposits. The analysis of environmental samples will be carried out using the instrument-analytical complex of Science and Production Association "Typhoon", which is equipped with a modern set of spectrometric, chromatographic and other instrumentation conforming to the international technical and scientific standards. The specific analysis of pollution of the environment by missile fuel and products of their metamorphosis will be carried out by experts from the Institute of Biophysics/State Scientific Centre, who also have extensive experience in this area.
For the representative subgroups of the military personnel and civilian residents, in total about 200 men, the frequency of structural somatic and gene mutations in blood cells, and also the immunological index will be analyzed simultaneously in accordance with the scheme described above. The samples of peripheral blood of study subjects and controls will be taken to MRRC, (Obninsk) for the laboratory investigation.
The detailed statistical analysis of the observed frequencies of chromosomal aberrations and gene mutations will permit scientifically justified conclusions concerning the presence or absence of risk and also about the nature of the risk factor: chemical or radiation. This will lead to identification of a subgroup of the study subjects with risk and thus indicate the need for ongoing detailed medical surveillance. Both military personnel and civilian residents who lived in the area for a long time would be included in such a subgroup.
By means of comprehensive analysis of environment pollution and mutation load indices of blood of the study groups, reliable conclusions will be formulated describing the effectiveness of clean-up activities performed in the vicinity of a given military base. This will input into the official decision taking concerning the possibility of exploitation of the terrain for peaceful economic activity by the local government bodies who take over the terrain for administrative managerial operation.
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