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Complex chromosome aberrations persist in individuals many years after occupational exposure to densely ionizing radiation: an mFISH study.

https://arctichealth.org/en/permalink/ahliterature174652
Source
Genes Chromosomes Cancer. 2005 Sep;44(1):1-9
Publication Type
Article
Date
Sep-2005
Author
M Prakash Hande
Tamara V Azizova
Ludmilla E Burak
Valentin F Khokhryakov
Charles R Geard
David J Brenner
Author Affiliation
Center for Radiological Research, Columbia University Medical Center, New York, USA.
Source
Genes Chromosomes Cancer. 2005 Sep;44(1):1-9
Date
Sep-2005
Language
English
Publication Type
Article
Keywords
Chromosome Aberrations - radiation effects
Chromosomes, Human - radiation effects
Humans
In Situ Hybridization, Fluorescence
Nuclear Reactors
Occupational Exposure
Plutonium
Radiation, Ionizing
Radon
Russia
Translocation, Genetic
Abstract
Long-lived, sensitive, and specific biomarkers of particular mutagenic agents are much sought after and potentially have broad applications in the fields of cancer biology, epidemiology, and prevention. Many clastogens induce a spectrum of chromosome aberrations, and some of them can be exploited as biomarkers of exposure. Densely ionizing radiation, for example, alpha particle radiation (from radon or plutonium) and neutron radiation, preferentially induces complex chromosome aberrations, which can be detected by the 24-color multifluor fluorescence in situ hybridization (mFISH) technique. We report the detection and quantification of stable complex chromosome aberrations in lymphocytes of healthy former nuclear-weapons workers, who were exposed many years ago to plutonium, gamma rays, or both, at the Mayak weapons complex in Russia. We analyzed peripheral-blood lymphocytes from these individuals for the presence of persistent complex chromosome aberrations. A significantly elevated frequency of complex chromosome translocations was detected in the highly exposed plutonium workers but not in the group exposed only to high doses of gamma radiation. No such differences were found for simple chromosomal aberrations. The results suggest that stable complex chromosomal translocations represent a long-lived, quantitative, low-background biomarker of densely ionizing radiation for human populations exposed many years ago.
PubMed ID
15912529 View in PubMed
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Past exposure to densely ionizing radiation leaves a unique permanent signature in the genome.

https://arctichealth.org/en/permalink/ahliterature185956
Source
Am J Hum Genet. 2003 May;72(5):1162-70
Publication Type
Article
Date
May-2003
Author
M Prakash Hande
Tamara V Azizova
Charles R Geard
Ludmilla E Burak
Catherine R Mitchell
Valentin F Khokhryakov
Evgeny K Vasilenko
David J Brenner
Author Affiliation
Center for Radiological Research, Columbia University, New York, NY 10032, USA.
Source
Am J Hum Genet. 2003 May;72(5):1162-70
Date
May-2003
Language
English
Publication Type
Article
Keywords
Alpha Particles - adverse effects
Bone Marrow - radiation effects
Chromosome Aberrations
Chromosome Breakage
Chromosome Inversion
Chromosome Painting
Chromosomes, Human - radiation effects - ultrastructure
Chromosomes, Human, Pair 5 - radiation effects - ultrastructure
Gamma Rays - adverse effects
Genome, Human
Humans
In Situ Hybridization, Fluorescence
Inhalation Exposure - adverse effects
Lymphocytes - pathology - radiation effects
Nuclear Reactors
Occupational Exposure - adverse effects
Plutonium - adverse effects
Radiation Dosage
Radiation, Ionizing
Reference Values
Russia
Time
Translocation, Genetic
USSR
Abstract
Speculation has long surrounded the question of whether past exposure to ionizing radiation leaves a unique permanent signature in the genome. Intrachromosomal rearrangements or deletions are produced much more efficiently by densely ionizing radiation than by chemical mutagens, x-rays, or endogenous aging processes. Until recently, such stable intrachromosomal aberrations have been very hard to detect, but a new chromosome band painting technique has made their detection practical. We report the detection and quantification of stable intrachromosomal aberrations in lymphocytes of healthy former nuclear-weapons workers who were exposed to plutonium many years ago. Even many years after occupational exposure, more than half the blood cells of the healthy plutonium workers contain large (>6 Mb) intrachromosomal rearrangements. The yield of these aberrations was highly correlated with plutonium dose to the bone marrow. The control groups contained very few such intrachromosomal aberrations. Quantification of this large-scale chromosomal damage in human populations exposed many years earlier will lead to new insights into the mechanisms and risks of cytogenetic damage.
Notes
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PubMed ID
12679897 View in PubMed
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Stable intrachromosomal biomarkers of past exposure to densely ionizing radiation in several chromosomes of exposed individuals.

https://arctichealth.org/en/permalink/ahliterature178301
Source
Radiat Res. 2004 Sep;162(3):257-63
Publication Type
Article
Date
Sep-2004
Author
Catherine R Mitchell
Tamara V Azizova
M Prakash Hande
Ludmilla E Burak
Josephine M Tsakok
Valentin F Khokhryakov
Charles R Geard
David J Brenner
Author Affiliation
Center for Radiological Research, Columbia University, New York, New York 10032, USA. cm2073@columbia.edu
Source
Radiat Res. 2004 Sep;162(3):257-63
Date
Sep-2004
Language
English
Publication Type
Article
Keywords
Aged
Aged, 80 and over
Body Burden
Chromosome Aberrations - radiation effects - statistics & numerical data
Chromosome Banding - methods
Chromosomes, Human - radiation effects
Dose-Response Relationship, Radiation
Female
Gamma Rays
Genetic Markers - radiation effects
Humans
Leukocytes - metabolism
Male
Middle Aged
Nuclear Reactors
Occupational Exposure - analysis
Plutonium
Radiation Dosage
Radiation, Ionizing
Radiometry - methods
Risk Assessment - methods
Risk factors
Russia - epidemiology
Abstract
A multicolor banding (mBAND) fluorescence in situ hybridization technique was used to investigate the presence inhuman populations of a stable biomarker-intrachromosomal chromosome aberrations-of past exposure to high-LET radiation. Peripheral blood lymphocytes were taken from healthy Russian nuclear workers occupationally exposed from 1949 onward to either plutonium, gamma rays or both. Metaphase spreads were produced and chromosomes 1 and 2 were hybridized with mBAND FISH probes and scored for intra-chromosomal aberrations. A large yield of intrachromosomal aberrations was observed in both chromosomes of the individuals exposed to high doses of plutonium, whereas there was no significant increase over the (low) background control rate in the population who were exposed to high doses of gamma rays. Interchromosome aberration yields were similar in both the high plutonium and the high gamma-ray groups. These results for chromosome 1 and 2 confirm and extend data published previously for chromosome 5. Intrachromosomal aberrations thus represent a potential biomarker for past exposure to high-LET radiations such as alpha particles and neutrons and could possibly be used as a biodosimeter to estimate both the dose and type of radiation exposure in previously exposed populations.
PubMed ID
15378838 View in PubMed
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Uncertainties analysis for the plutonium dosimetry model, doses-2005, using Mayak bioassay data.

https://arctichealth.org/en/permalink/ahliterature161923
Source
Health Phys. 2007 Sep;93(3):207-19
Publication Type
Article
Date
Sep-2007
Author
John D Bess
Melinda P Krahenbuhl
Scott C Miller
David M Slaughter
Viktor V Khokhryakov
Valentin F Khokhryakov
Klara G Suslova
Vadim V Vostrotin
Author Affiliation
Center for Excellence in Nuclear Technology, Engineering, and Research (CENTER), 50 So. Central Campus Drive, Rm 1206, University of Utah, Salt Lake City, UT 84112, USA.
Source
Health Phys. 2007 Sep;93(3):207-19
Date
Sep-2007
Language
English
Publication Type
Article
Keywords
Air Pollutants, Radioactive
Autopsy
Biological Assay
Cohort Studies
Humans
Models, Theoretical
Monte Carlo Method
Occupational Exposure
Plutonium - urine
Radiation Dosage
Radiometry
Russia
Smoking
Uncertainty
Abstract
The Doses-2005 model is a combination of the International Commission on Radiological Protection (ICRP) models modified using data from the Mayak Production Association cohort. Surrogate doses from inhaled plutonium can be assigned to approximately 29% of the Mayak workers using their urine bioassay measurements and other history records. The purpose of this study was to quantify and qualify the uncertainties in the estimates for radiation doses calculated with the Doses-2005 model by using Monte Carlo methods and perturbation theory. The average uncertainty in the yearly dose estimates for most organs was approximately 100% regardless of the transportability classification. The relative source of the uncertainties comes from three main sources: 45% from the urine bioassay measurements, 29% from the Doses-2005 model parameters, and 26% from the reference masses for the organs. The most significant reduction in the overall dose uncertainties would result from improved methods in bioassay measurement with additional improvements generated through further model refinement. Additional uncertainties were determined for dose estimates resulting from changes in the transportability classification and the smoking toggle. A comparison was performed to determine the effect of using the model with data from either urine bioassay or autopsy data; no direct correlation could be established. Analysis of the model using autopsy data and incorporation of results from other research efforts that have utilized plutonium ICRP models could improve the Doses-2005 model and reduce the overall uncertainty in the dose estimates.
Notes
Comment In: Health Phys. 2008 Jun;94(6):581-3; author reply 583-418469592
PubMed ID
17693771 View in PubMed
Less detail