Active Projects in the Russian Health Studies Program
Studies on the health effects of
radiation exposure are conducted jointly by U.S. and Russian
scientists at Mayak and the Southern Urals Biophysics Institute
in Ozersk and at the Urals Research Center for Radiation Medicine
in Chelyabinsk. U.S. organizations involved in the studies are:
- Columbia University;
- Los Alamos National Laboratory;
- Lovelace Respiratory Research Institute;
- National Cancer Institute;
- Pacific Northwest National Laboratory;
- University of Illinois at Chicago; and
- University of Utah.
Russian organizations leading the studies are:
- Mayak Production Association;
- Southern Urals Biophysics Institute; and
- Urals Research Center for Radiation Medicine.
The program is organized into three directions: community, worker,
and emergency response.
Direction
1: Community Health Effects Research
The major goal under this Direction is to analyze the carcinogenic
risk of radiation exposure. For this purpose, 3 projects are
being conducted:
- Project 1.1, Techa River Population Dosimetry;
- Project 1.2b, Techa River Population Morbidity; and
- Project 1.4, Reconstruction of Dose to the Residents of
Ozersk.
Project 1.1: Techa River Population Dosimetry
Principal Investigators:
R.F.: Marina Degteva,
Urals Research Center for Radiation Medicine
U.S.: Lynn Anspaugh, University
of Utah
Brief Description: This dose reconstruction project
is to develop improvements in the existing Techa River Dosimetry
System 2000 for the members of the Extended Techa River Cohort
(ETRC) by reducing the uncertainty of the doses, validating
the doses, determining the feasibility of reconstructing doses
from medical exposures, and reconstructing doses from other
sources of radiation exposure, such as the East Urals Radioactive
Trace and resuspension from deposits in Lake Karachai. The
specific goal of this project is to update the reconstruction
of external and internal radiation doses for approximately
30,000 individuals in the ETRC for use in companion epidemiologic
studies of radiogenic leukemia and solid cancers (see below
Project 1.2b, Techa River Population Morbidity).
Results to date: The specific aim of the completed
phase of this project was to enhance reconstruction of doses
for the ETRC cohort members. The database of preliminary village-average
doses was expanded and upgraded to individualized doses and
the uncertainty in the reconstructed doses was evaluated for
the first time.
Projected end date: September 2009.
Project 1.2b: Techa River Population Morbidity
Principal Investigators:
R.F.: Alexander Akleyev,
Urals Research Center for Radiation Medicine
U.S.: Faith Davis, University of Illinois at Chicago
Brief Description: This epidemiologic study is designed
to assess carcinogenic effects among populations exposed to
offsite releases of radioactive materials from the Mayak nuclear
facility. Discharges of radioactive wastes into the Techa
River during the period 1950-1956 resulted in radiation exposures
of the inhabitants of the riverside villages for whom the
river was the principal source of water. This is the first
study of cancer morbidity in the extended Techa River cohort
(ETRC). It is a companion study to Project 1.1, Techa River
Population Dosimetry, and to Techa River Population Mortality,
sponsored by the U.S. National Cancer Institute. The aim of
Phase III is to extend the follow-up of cancer incidence among
the members of the ETRC and use new epidemiological and dosimetric
data from Project 1.1 to assess radiogenic cancer risk.
Results to date: Preliminary results from this study
indicate an increased incidence of leukemia and stomach cancer
in the exposed population.
Projected end date: September 2009.
Project 1.4: Reconstruction of
Dose to the Residents of Ozersk
R.F.: Yuri Mokrov, Mayak
U.S.: Lynn Anspaugh, University
of Utah
Brief Description: Phase II of this dose reconstruction
project is to reconstruct time-dependent individual radiation
doses to the residents of the city of Ozersk, Russia, and
the surrounding area from atmospheric releases of radionuclides
from nuclear weapons production activities at Mayak from 1948
to present. Focus will be on the emission of I-131 and dose
to the thyroid glands of children. Data will support the epidemiologic
study of thyroid cancer in children sponsored by the National
Cancer Institute. This should help resolve the dichotomy between
the studies at Hanford (no observed effect) and Chernobyl
(large effect). The data also will determine whether these
emissions are a confounding factor in the evaluation of radiogenic
cancer risk in other groups under study, such as the Extended
Techa River Cohort (Project 1.2b) and the Mayak worker cohort
(Project 2.2).
Results to date: The Phase I feasibility study was
completed on March 31, 2004 and a final report was prepared.
For the first time, an estimate of the atmospheric stack releases
of I-131 was prepared by month from the two fuel-processing
plants.
Projected end date: September 2008.
Project 2.2: Mayak Worker
Epidemiology
Principal Investigators:
R.F.: Mikhail Sokolnikov, Southern Urals Biophysics Institute
U.S.: Ethel Gilbert, National Cancer Institute
Brief Description: This epidemiologic study is designed
to obtain quantitative estimates of carcinogenic risks from
both protracted external exposure and from internal exposure
to plutonium based on analyses of data from the Mayak worker
cohort. The cohort consists of 26,000 workers first employed
at any time between 1948 and 1982. Vital status is known through
2000. Risks of cancers of the lung, liver, and bone are being
expressed as functions of doses to these organs and of potential
modifying factors such as sex, time since exposure, and age
at exposure. In addition, researchers will investigate whether
risks of cancers of sites other than lung, liver, and bone
are related to external dose and to plutonium exposure. Uncertainties
in risk estimates that are developed will be quantified. In
order to meet these objectives, further improvements in the
data are being implemented. These include the continual updating
of follow-up and the collection of further data on smoking
from medical records. The results of this study are likely
to enhance our understanding of protracted radiation exposure
risks to humans and provide definitive data for the improvement
and validation of radiation protection standards.
Results to date: This is the first study to demonstrate
a statistically significant association between occupational
exposure to plutonium and bone, lung, and liver cancer. These
analyses were performed using the Mayak worker Doses 2000
database. Now that the Project 2.4 dosimetrists have completed
the "Doses 2005" database, Project 2.2 researchers will analyze
the data using the most recent dose estimates and compute
new cancer risk estimates linked to radiation dose.
Projected end date: September 2009.
Project 2.4: Mayak Worker Dosimetry
Principal Investigators:
R.F.: Evgeny Vasilenko (External Dosimetry Team Leader), Mayak and Victor Khokhryakov
(Internal Dosimetry Team Leader), Southern Urals Biophysics Institute
U.S.: Scott Miller, University of Utah, Robert Scherpelz (External
Dosimetry Team Leader), Pacific Northwest National Laboratory, and Melinda
Krahenbuhl (Internal Dosimetry Team Leader), University of
Utah
Brief Description: This dose reconstruction project
is to establish a computerized database of individual internal
and external radiation doses and uncertainty about those doses
for each member of the 26,000 Mayak worker cohort under study
in Project 2.2, Mayak Worker Epidemiology. The work product
will be an electronic database containing updated individual
dose estimates by year called "Doses 2008." As a result, improved
doses for risk assessment analysis of causes of health effects
from radiation exposure will be available. These data are
also being used for other projects in Direction 2. This project
is perhaps one of the most important of the 9 current projects
within the Russian Health Studies Program. Without good dosimetry
data, epidemiologists and biostatisticians will not be able
to assess radiation-induced cancer risks from exposure to
gamma, neutron, and alpha radiation. The Mayak worker cohort
under study has the largest number of individuals and the
highest chronic radiation exposures of any known population
on earth. Approximately one-fourth of the exposed workers were
women. Detailed health and exposure records are available
at Mayak, thereby facilitating radiation health effects research.
Results to date: In addition to providing the dosimetric
data for Project 2.2, Mayak Worker Epidemiology, this project
has enhanced the understanding of plutonium metabolism in
the human body and improved the biokinetic models for assessing
dose from plutonium uptakes. These outcomes will be of direct
benefit to DOE in improving the determination of dose to DOE
workers from plutonium exposure. Improved doses have been
calculated for a fraction of the group of workers. Dose calculations
and uncertainty analysis of the doses continues. The Mayak
worker dosimetry database "Doses 2005" was completed in 2005.
Project 2.2 researchers will analyze the data using the most
recent dose estimates and will produce revise radiation cancer
risk estimates by September 2006.
Projected end date: September 2008.
Project
2.4 Team members in Ozersk, Russia: Dong-Ok Choe (external
dosimetry), Melinda Krahenbuhl (U.S. internal dosimetry team
leader), Scott Miller (U.S. Principal Investigator), John
Fix (former U.S. external dosimetry team leader), Robert Scherpelz
(new U.S. external dosimetry team leader), and Alexander Danilov (interpreter)
(2003).
Project 2.5: Improved Plutonium Dose Assessment
Methods in Mayak Workers
Principal Investigators:
R.F.: Sergey Romanov, Southern Urals Biophysics Institute
U.S.: Raymond Guilmette, Los Alamos National Laboratory
Brief Description: In phase III, researchers developed
and implemented an effective, improved modeling approach for estimating
organ doses to individual Mayak workers and linked best central estimates of
dose with quantitative measures of uncertainty in the doses. In addition,
investigators used Monte Carlo computational methods to calculate alpha particle
radiation dose and dose rate patterns in the parenchymal regions of the
lung so as to evaluate the extent and magnitude of non-uniformity of radiation
dose delivered to this region of the lung. The main objective of phase IV of
Project 2.5 is to obtain new knowledge and implement additional tools that
will facilitate the development of a new harmonized plutonium dosimetry system,
which will eventually replace the Mayak Worker Doses 2005 dosimetry system in
Project 2.4, Mayak Worker Dosimetry. This includes: 1) experimentally
addressing several issues that are crucial for lung dosimetry modeling, i.e.,
assessing the dose contribution from submicron alpha-emitting aerosols in the
air of Mayak workplaces; further validating the fixed plutonium compartment and
its incorporation into the physiologically realistic plutonium biokinetic model
for lung; and evaluating the rapid absorption of plutonium from the lungs into
the blood; 2) combining plutonium dose estimates with the uncertainties for
individual Mayak workers by using available urine bioassay and/or postmortem
tissue data together with the Bayesian approach implemented as the LANL/SUBI
IMPDOS III computer code for individual dose assessment; and 3) applying the
probability distributions for intake and biokinetic model parameters to assess
the dose for workers monitored for plutonium to Mayak worker cohort members for
whom little or no plutonium monitoring data are available.
Results to date: This project is provided valuable insights into the
radiobiology and dosimetry of plutonium sequestered for decades in the lungs of
Mayak workers. It was the first study to demonstrate in humans that inhaled
plutonium is sequestered in the lung parenchyma. This information is being used
to modify the human respiratory tract dosimetry models for improved lung dosimetry.
In Phase II, microscopic analyses of the distribution of plutonium in the lungs
of 24 Mayak workers showed that there was significantly more plutonium retained
in the parenchymal regions of the lung than was predicted using either ICRP 66
or ICRP 30 respiratory tract dosimetry models. This long-term retention occurred
for both allegedly more soluble and less soluble forms of the inhaled plutonium
aerosol. Although in some cases, the fraction of plutonium remaining in lung
was a small fraction of the plutonium body burden at death, this portion still
contributed a significant amount of the total radiation dose to lung because of
its very long retention time, i.e., decades after exposure. The consequence of
underestimating the lung dose is that it leads to overestimating the risk
coefficient per unit dose for radiation-induced lung diseases in epidemiological
studies. Thus, using models that do not accurately represent the central values
of dose for a population of measured data will introduce bias into the dose and
risk assessment.
Projected end date: September 2010.
Project 2.6: Molecular Markers
of Lung Cancer in Mayak Workers
Principal Investigators:
R.F.: Vitaliy
Telnov, Southern Urals Biophysics Institute
U.S.: Steve Belinsky, Lovelace Respiratory Research Institute
Brief Description: This molecular epidemiology study
is to test for existence of early molecular markers of lung
cancer due from radiation exposure following the inhalation
of airborne plutonium. The first working hypothesis is that
the frequency of methylation of the CpG islets of MGMT, p16,
DAP-kinase, RASSF1A, and other genes in adenocarcinomas and
squamous cell carcinomas is higher in plutonium-exposed workers
than in unexposed subjects. The second working hypothesis
is that the abnormal methylation of critical regulatory genes
of carcinogenesis serves as a biomarker for the pre-clinical
diagnosis of lung cancer in living plutonium-exposed workers.
Results to date: The original project demonstrated
that plutonium plant workers with adenocarcinoma of the lung,
when compared to controls and after adjustment for age and
gender, had a statistically significant increased risk of
methylation of the p16 tumor suppressor gene. This means that
the gene designed to prevent lung cancer was inactivated by
the exposure to inhaled plutonium. The current phase of the
research is to examine methylation profiles in both adenocarcinomas
and squamous cell carcinomas of the lung and to begin population-based
studies in former Mayak workers. Given the renewed threat
of nuclear terrorism following the tragedy of September 11,
2001, follow-up studies will determine whether specific methylation
changes could be evaluated as intermediate biomarkers in risk
assessment of persons exposed to radiation.
Projected end date: September 2008.
Project 2.7: Radiation Biomarkers
Principal Investigators:
R.F.: Tamara Azizova, Southern Urals Biophysics Institute
U.S.: David Brenner, Columbia University
Brief Description: This molecular epidemiology study
is to develop a new biological dosimetry test using blood
samples to determine internal and external radiation exposures.
More specifically, by analyzing heritable changes in chromosomes
in blood samples from Mayak workers exposed to different combinations
of external and internal radiation for many years, the investigators
will develop a calibrated test that will provide an estimate
of both the internal and external ionizing radiation doses.
Such a biomarker would significantly increase the power of
epidemiologic studies of individuals exposed to densely-ionizing
radiations, such as alpha particles, e.g., radon, plutonium
workers, or neutrons, e.g., DOE/NRC workers, airline personnel.
Ultimately, the blood test will be submitted to the U.S. Food
and Drug Administration for approval.
Results to date: This study was the first to demonstrate
a statistically significant dose-response between plutonium
exposure and intra-arm chromosomal aberrations from worker
blood samples. In fact, the test was sensitive enough to distinguish
internal from external exposures. The current research is
focused on calibrating the doses with the effects so as to
develop a blood test for use in the nuclear, airline, and
aerospace industries.
Projected end date: September 2008.
Project
2.8: Mayak Worker Tissue Repository
Principal Investigators:
R.F.: Klara Muksinova, Southern Urals Biophysics Institute
U.S.: Christopher Loffredo, Georgetown University
Brief Description: The aim of this project is to
establish and maintain a state-of-the-art tissue repository
designed to serve as a resource for studies of the effects
of protracted internal and external radiation exposure on
human health. Presently, the repository is located at the
Southern Urals Biophysics Institute in Ozersk. It includes
samples of archival autopsy tissues from 800 registrants,
samples of surgical tissues from more than 250 individuals,
and samples of blood and its components from about 1,600 Mayak
workers. The storage conditions of the biosamples in the repository
were designed to provide optimal long-term preservation of
tissue samples. In conjunction with medical, occupational,
and dosimetry information, data collected in the repository
are used in molecular epidemiology studies. Such studies can
be used to establish an association between disease and radiation
exposure in individuals.
Results to date: Samples of tumor and other tissues
for 155 registrants were delivered to the U.S. researchers
working on several projects in the Russian Health Studies
Program, i.e., Project 2.5, Plutonium Microdosimetry in the
Lung, Project 2.6, Molecular Markers of Lung Cancer, and Project
2.7, Radiation Biomarkers. Methods of transportation of tissue
samples from Russia to other countries by international air
mail have been tested and implemented. A website
in both Russian and English describes the contents of the
repository and the procedures for researcher access to the contents.
Further collection and storage of tissue samples in optimal conditions
and intensification of efforts to inform scientists worldwide on
the established repository and its biosamples are underway.
Projected end date: September 2012.
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This page was last updated on February 12, 2008
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