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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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High prevalence of RET rearrangement in thyroid tumors of children from Belarus after the Chernobyl reactor accident.

https://arctichealth.org/en/permalink/ahliterature22965
Source
Oncogene. 1995 Dec 21;11(12):2459-67
Publication Type
Article
Date
Dec-21-1995
Author
S. Klugbauer
E. Lengfelder
E P Demidchik
H M Rabes
Author Affiliation
Institute of Pathology, Ludwig Maximillyians University of Munich, Germany.
Source
Oncogene. 1995 Dec 21;11(12):2459-67
Date
Dec-21-1995
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adult
Base Sequence
Carcinoma, Papillary - genetics
Child
Child, Preschool
Drosophila Proteins
Female
Gene Rearrangement
Humans
Infant
Male
Middle Aged
Molecular Sequence Data
Neoplasms, Radiation-Induced - genetics
Nuclear Reactors
Polymerase Chain Reaction
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins c-ret
Proto-Oncogenes
Receptor Protein-Tyrosine Kinases - genetics
Research Support, Non-U.S. Gov't
Thyroid Neoplasms - etiology - genetics
Ukraine
Abstract
RET rearrangement was studied in papillary thyroid carcinomas (PTC) of children exposed to radioactive fallout in Belarus after the Chernobyl accident. To detect RET rearrangement in small tissue samples from thyroidectomy specimen (12 PTC of children; 2 PTC and 1 follicular carcinoma of adults; non-tumorous thyroid tissue of 4 children and 4 adults as controls), a RT-multiplex PCR was developed using primers suited to amplify fragments in different quantities depending on the presence or absence of RET rearrangements in the tissues. The type of rearrangement was determined by RT-PCR and direct sequencing using primers for ret/PTC1, 2 and 3. Two-thirds of the papillary thyroid carcinomas of the children revealed a RET rearrangement, with ret/PTC3 being more frequent by a factor of 3 than ret/PTC1. ret/PTC2 was not detected. All RET rearrangement-positive tumors had lymph node metastasis while half of the tumors with wild-type cRET had not. More than half of the cases with ret/PTC3 expressed not only the ELE/RET transcript as expected, but also the RET/ELE transcript. Intrachromosomal rearrangement involving RET and the adjacent H4 or ELE gene on chromosome no. 10 is a very frequent event in thyroid cancer of children of the Chernobyl-contaminated zone of Belarus.
PubMed ID
8545102 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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Revisiting nuclear power plant safety.

https://arctichealth.org/en/permalink/ahliterature18690
Source
Science. 2003 Jan 10;299(5604):201-3; author reply 201-3
Publication Type
Article
Date
Jan-10-2003
Author
David J Brenner
Source
Science. 2003 Jan 10;299(5604):201-3; author reply 201-3
Date
Jan-10-2003
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Humans
Neoplasms, Radiation-Induced - epidemiology - etiology
Nuclear Energy
Nuclear Reactors
Power Plants
Radiation Dosage
Terrorism
Ukraine - epidemiology
United States
Notes
Comment On: Science. 2002 Sep 20;297(5589):1997-912242425
PubMed ID
12523358 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
Less detail
Source
Nature. 1992 Sep 3;359(6390):21
Publication Type
Article
Date
Sep-3-1992
Author
V S Kazakov
E P Demidchik
L N Astakhova
Source
Nature. 1992 Sep 3;359(6390):21
Date
Sep-3-1992
Language
English
Publication Type
Article
Keywords
Accidents
Child
Humans
Neoplasms, Radiation-Induced - epidemiology
Nuclear Reactors
Thyroid Neoplasms - epidemiology
Ukraine
Notes
Comment In: Nature. 1992 Oct 22;359(6397):680-11436030
Comment In: Nature. 1992 Oct 22;359(6397):6811436031
Comment In: Nature. 1992 Sep 3;359(6390):21-21522880
PubMed ID
1522879 View in PubMed
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Time trends of thyroid cancer incidence in Belarus after the Chernobyl accident.

https://arctichealth.org/en/permalink/ahliterature21049
Source
Radiat Res. 1999 May;151(5):617-25
Publication Type
Article
Date
May-1999
Author
W F Heidenreich
J. Kenigsberg
P. Jacob
E. Buglova
G. Goulko
H G Paretzke
E P Demidchik
A. Golovneva
Author Affiliation
GSF-National Research Center for Environment and Health, Institute for Radiation Protection, Neuherberg, Germany.
Source
Radiat Res. 1999 May;151(5):617-25
Date
May-1999
Language
English
Publication Type
Article
Keywords
Accidents, Radiation
Adolescent
Adult
Age Factors
Byelarus - epidemiology
Child
Child, Preschool
Female
Humans
Incidence
Infant
Male
Neoplasms, Radiation-Induced - epidemiology
Nuclear Reactors
Power Plants
Research Support, Non-U.S. Gov't
Sex Factors
Thyroid Neoplasms - epidemiology
Time Factors
Ukraine
Abstract
The rates of childhood thyroid cancer incidence observed in Belarus during the period 1986 to 1995 are described as a function of time after exposure, age at exposure, and sex. Conclusions are drawn for the excess absolute risk function. After a minimum latent period of about 3 years after exposure, this risk function has a linear increase with time for at least 6 years. After correction for the dependence of average doses on age, the radiation-induced absolute thyroid risk in Gomel is about a factor of 3 higher for children up to age 10 at exposure compared to older ones; this may be due in part to different case-collection quality. In addition, in the group up to 10 years at exposure, the thyroid of girls is more sensitive to radiation by a factor of about 1.5 than the thyroid of boys on an absolute scale. Risk estimates from external exposure are consistent with risk estimates from Gomel assuming that the increase in excess cases reaches a plateau soon.
PubMed ID
10319735 View in PubMed
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7 records – page 1 of 1.