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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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Thyroid nodularity and cancer among Chernobyl cleanup workers from Estonia.

https://arctichealth.org/en/permalink/ahliterature22224
Source
Radiat Res. 1997 Feb;147(2):225-35
Publication Type
Article
Date
Feb-1997
Author
P D Inskip
M F Hartshorne
M. Tekkel
M. Rahu
T. Veidebaum
A. Auvinen
L A Crooks
L G Littlefield
A F McFee
S. Salomaa
S. Makinen
J D Tucker
K J Sorensen
W L Bigbee
J D Boice
Author Affiliation
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20892, USA.
Source
Radiat Res. 1997 Feb;147(2):225-35
Date
Feb-1997
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adenocarcinoma, Follicular - epidemiology - etiology - pathology
Adult
Biopsy, Needle
Carcinoma, Papillary - epidemiology - etiology - pathology
Chromosomes, Human - radiation effects
Cohort Studies
Erythrocyte Membrane - chemistry
Estonia - epidemiology
Glycophorin - genetics
Humans
Lymphocytes - ultrastructure
Male
Middle Aged
Neoplasms, Radiation-Induced - epidemiology - etiology - pathology - ultrasonography
Occupational Exposure
Population Surveillance
Power Plants
Prevalence
Radiation monitoring
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Thyroid Gland - radiation effects
Thyroid Neoplasms - epidemiology - etiology - pathology - ultrasonography
Thyroid Nodule - epidemiology - etiology - pathology - ultrasonography
Translocation, Genetic
Ukraine
Abstract
Thyroid examinations, including palpation, ultrasound and, selectively, fine-needle aspiration biopsy, were conducted on nearly 2,000 Chernobyl cleanup workers from Estonia to evaluate the occurrence of thyroid cancer and nodular thyroid disease among men with protracted exposure to ionizing radiation. The examinations were conducted in four cities in Estonia during March-April 1995, 9 years after the reactor accident. The study population was selected from a predefined cohort of 4,833 cleanup workers from Estonia under surveillance for cancer incidence. These men had been sent to Chernobyl between 1986 and 1991 to entomb the damaged reactor, remove radioactive debris and perform related cleanup activities. A total of 2,997 men were invited for thyroid screening and 1,984 (66%) were examined. Estimates of radiation dose from external sources were obtained from military or other institutional records, and details about service dates and types of work performed while at Chernobyl were obtained from a self-administered questionnaire. Blood samples were collected for assay of chromosomal translocations in circulating lymphocytes and loss of expression of the glycophorin A (GPA) gene in erythrocytes. The primary outcome measure was the presence or absence of thyroid nodules as determined by the ultrasound examination. Of the screened workers, 1,247 (63%) were sent to Chernobyl in 1986, including 603 (30%) sent in April or May, soon after the accident. Workers served at Chernobyl for an average of 3 months. The average age was 32 years at the time of arrival at Chernobyl and 40 years at the time of thyroid examination. The mean documented radiation dose from external sources was 10.8 cGy. Biological indicators of exposure showed low correlations with documented dose, but did not indicate that the mean dose for the population was higher than the average documented dose. Ultrasound examinations revealed thyroid nodules in 201 individuals (10.2%). The prevalence of nodules increased with age at examination, but no significant associations were observed with recorded dose, date of first duty at Chernobyl, duration of service at Chernobyl, building the sarcophagus or working on the roof of neighboring buildings or close to the damaged reactor. Nodularity showed a nonsignificant (p(1) = 0.10) positive association with the proportion of lymphocytes with chromosome translocations, but associations with the frequency of variant erythrocytes in the GPA assay were weak and unstable (p(1) > or = 0.46). The majority of fine-needle biopsies taken on 77 study participants indicated benign nodular disease. However, two cases of papillary carcinoma and three benign follicular neoplasms were identified and referred for treatment. Both men with thyroid cancer had been sent to Chernobyl in May of 1986, when the potential for exposure to radioactive iodines was greatest. Chernobyl cleanup workers from Estonia did not experience a markedly increased risk of nodular thyroid disease associated with exposure to external radiation. Possible reasons for the apparent absence of effect include low radiation doses, the protracted nature of the exposure, errors in dose measurement, low sensitivity of the adult thyroid gland or the insufficient passage of time for a radiation effect to be expressed.
PubMed ID
9008215 View in PubMed
Less detail