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カテゴリー「genetics / gene mutation」

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

Title: High prevalence of RET rearrangement in thyroid tumors of children from Belarus after the Chernobyl reactor accident
Author:Klugbauer S., Lengfelder E., Demidchik E.P., Rabes H.M.
Reference:Oncogene N 12, 1995, т.11, стр.2459-2467
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Radiobiological evaluation of immigrants from the vicinity of Chernobyl.

Title: Radiobiological evaluation of immigrants from the vicinity of Chernobyl.

Author: Livingston GK, Jensen RH, Silberstein EB, Hinnefeld JD, Pratt G, Bigbee WL, Langlois RG, Grant SG, Shukla R

Reference: Int J Radiat Biol 1997, 72:703–713.

doi:10.1080/095530097142861

Keywords :

Abstract: Eighty individuals (55 adults and 25 children) who were residents of four cities (Kiev, Mozyr, Gomel and Bobrujsk) located 100-200 km from Chernobyl at the time of the accident in 1986 were tested after immigrating to the US from 1989-1991. A whole-body counter was employed to quantitate radiocesium content. In addition, two biological measures of radiation effects, namely, chromosomal integrity using the micronucleus assay and somatic mutation analysis of erythrocytes at the glycophorin A (GPA) locus, were applied to this group. Radiocesium activity in the body ranged from 0 to 56.8 Bq/kg with a mean and standard deviation of 5.0 8.2 and a median value of 2.0 Bq/kg. Mean radiocesium content by groups was highest in adult males (9.0 11.7; range 0.21-56.8 Bq/kg) followed by adult females (3.3 4.5; range 0-21.3 Bq/kg), male children (3.0 5.7; range 0-20.2 Bq/kg) and lowest in female children (1.6 3.5; range 0-12.7 Bq/kg). Individuals with the highest radiocesium content in each group belonged to one family that lived in Mozyr (100 km from Chernobyl) until emigrating in 1989. The frequency of lymphocyte micronuclei and erythrocyte GPA alleleloss (O/N) somatic mutations were both significantly correlated with radiocesium content (r 0.57, p 0.002; r 0.75, p 0.002, respectively). The micronucleus frequency also correlated with the estimated internal absorbed dose from radiocesium in a subset of 20 immigrants for whom this calculation was possible (r 0.71, p 0.0005). Altogether, the biomonitoring data indicate that some subjects had radiation doses sufficient to produce gene and chromosomal mutations in blood cells, although these effects cannot be attributed solely to radiocesium exposure.

URL: http://informahealthcare.com/doi/abs/10.1080/095530097142861

A more comprehensive application of the micronucleus technique for biomonitoring of genetic damage rates in human populations – experiences from the Chernobyl catastrophe.

Title: A more comprehensive application of the micronucleus technique for biomonitoring of genetic damage rates in human populations – experiences from the Chernobyl catastrophe.

Author: Fenech M, Perepetskaya G, Mikhalevich L

Reference: Environ Mol Mutagen 1997, 30:112–118.

DOI: 10.1002/(SICI)1098-2280(1997)30:2<112::AID-EM3>3.0.CO;2-P

Keywords : micronucleus technique, lymphocytes, cytokinesis-block method, apoptosis, transgenerational effect; Chernobyl catastrophe

Abstract: The current method for scoring micronuclei as a measure of genetic damage rate in peripheral blood cells is to enumerate this end point in cytokinesis-blocked binucleated cultured lymphocytes. However, one can expect that, due to chronic exposure to genotoxins or inherent genetic instability, micronuclei may be expressed continually in vivo in dividing cell populations such as the progenitor cell lineages leading to mature lymphocytes or erythrocytes. Consequently, micronuclei may already be expressed in peripheral blood lymphocytes prior to culture. In view of these considerations, we have performed a study in children living in regions of Belarus that are contaminated by radionuclides from the Chernobyl disaster and compared their micronucleus frequency in erythrocytes, nondivided lymphocytes, and cultured cytokinesis-blocked binucleated lymphocytes to that of controls living in noncontaminated areas. Preliminary data presented in this paper indicate a significant two- to fourfold increase in micronucleus expression (P < 0.05) in exposed children relative to controls in erythrocytes or peripheral blood lymphocytes in blood smears as well as in mononuclear and cytokinesis-blocked binucleated lymphocytes in cultures. The measurement of micronuclei in nondivided mononuclear lymphocytes represents chromosomal damage expressed during in vivo divisions. The micronuclei in binucleated cultured cells represent micronuclei expressed ex-vivo and may include micronuclei already present in a cell prior to tissue culture. These preliminary data suggest that a different spectrum and level of damage may be observed in nondivided mononuclear lymphocytes, binucleated lymphocytes, and erythrocytes and that a combination of these approaches may provide a more comprehensive assessment of the extent of genetic damage induced by chronic exposure to radionuclides or other genotoxins in haematopoietic tissue.

URL: http://onlinelibrary.wiley.com/doi/10.1002/%28SICI%291098-2280%281997%2930:2%3C112::AID-EM3%3E3.0.CO;2-P/abstract;jsessionid=FD95AFCDA08A32206E545260A5FC08DF.f02t01

Sensorimotor Reactivity of Children Living in a Radionuclide-Contaminated Zone

Title: Sensorimotor Reactivity of Children Living in a Radionuclide-Contaminated Zone

Author: A. I. Kienya, O. V. Kirichenko

Reference: Human Physiology , March 2001, Volume 27, Issue 2, pp 216-220

DOI: 10.1023/A:1011087518862

Keywords :

Abstract: Schoolchildren aged 8 to 13 years were examined in Gomel. The children’s sensorimotor reaction to light and acoustic stimuli is characterized with regard for their age and sex on the basis of the latency of sensorimotor reactions (LSMR), which shortened significantly with age in children of either sex. This developed unevenly in the children examined, as may be seen from the quite broad ranges of the LSMR fluctuation in each age group. The boys had a stronger sensorimotor reaction to both light and acoustic stimuli than the girls. At the same time, both the boys and the girls reacted to the acoustic stimulus more actively than to the light stimulus.

URLhttp://link.springer.com/article/10.1023/A%3A1011087518862

Radioadaptive Response Following In Utero Low-Dose Irradiation

Title: Radioadaptive Response Following In Utero Low-Dose Irradiation

Author: Eric K. Howell, Sergey P. Gaschak, Kenneth D. W. Griffith and Brenda E. Rodgers

Reference: Radiation Research January 2013 : Vol. 179, Issue 1 (Jan 2013), pg(s) 29-37

DOI: 10.1667/RR3029.1

Keywords : In Utero, low-dose irradiation, DNA damage

Abstract: Acute radiation exposure is known to cause biological damage that leads to severe health effects. However, the effects and subsequent health implications of exposure to low doses of ionizing radiation are unclear. The purpose of this study was to investigate the effects of low-dose ionizing radiation exposures in utero. Pregnant laboratory mice (BALB/c) were exposed to low-dose Chernobyl radiation [10–13 mSv per day for 10 days] during organogenesis. The progeny were born and weaned in an uncontaminated laboratory, then were exposed to an acute radiation dose (2.4 Sv). Analysis of our end points (litter dynamics, DNA damage, bone marrow stem cell function, white blood cell counts and gene expression) suggests that a low-dose (100–130 mSv) in utero exposure to ionizing radiation is not deleterious to the offspring. Rather DNA damage, white blood cell levels, and gene expression results suggest a radioadaptive response was elicited for the in utero exposure with respect to the effects of the subsequent acute radiation exposure.

URLhttp://www.bioone.org/doi/abs/10.1667/RR3029.1?prevSearch=chernobyl&searchHistoryKey=&queryHash=f7283fdb5d57d03bfdb1eb17f03c59a5

Three Somatic Genetic Biomarkers and Covariates in Radiation-Exposed Russian Cleanup Workers of the Chernobyl Nuclear Reactor 6–13 Years after Exposure

Title: Three Somatic Genetic Biomarkers and Covariates in Radiation-Exposed Russian Cleanup Workers of the Chernobyl Nuclear Reactor 6–13 Years after Exposure

Author: Irene M. Jones, Heather Galick, Paula Kato, Richard G. Langlois, Mortimer L. Mendelsohn, Gloria A. Murphy, Pavel Pleshanov, Marilyn J. Ramsey, Cynthia B. Thomas, James D. Tucker, Ludmila Tureva, Irina Vorobtsova, and David O. Nelson

Reference: Radiation Research 158(4):424-442. 2002

DOI: http://dx.doi.org/10.1667/0033-7587(2002)158[0424:TSGBAC]2.0.CO;2

Keywords : cleanup workers, genetic biomarkers

Abstract: Three somatic mutation assays were evaluated in men exposed to low-dose, whole-body, ionizing radiation. Blood samples were obtained between 1992 and 1999 from 625 Russian Chernobyl cleanup workers and 182 Russian controls. The assays were chromosome translocations in lymphocytes detected by FISH, hypoxanthine phosphoribosyltransferase (HPRT) mutant frequency in lymphocytes by cloning, and flow cytometic assay for glycophorin A (GPA) variant frequency of both deletion (N/Ø) and recombination (N/N) events detected in erythrocytes. Over 30 exposure and lifestyle covariates were available from questionnaires. Among the covariates evaluated, some increased (e.g. age, smoking) and others decreased (e.g. date of sample) biomarker responses at a magnitude comparable to Chernobyl exposure. When adjusted for covariates, exposure at Chernobyl was a statistically significant factor for translocation frequency (increase of 30%, 95% CI of 10%–53%, P = 0.002) and HPRT mutant frequency (increase of 41%, 95% CI of 19%–66%, P < 0.001), but not for either GPA assay. The estimated average dose for the cleanup workers based on the average increase in translocations was 9.5 cGy. Translocation analysis is the preferred biomarker for low-dose radiation dosimetry given its sensitivity, relatively few covariates, and dose–response data. Based on this estimated dose, the risk of exposure-related cancer is expected to be low.

URLhttp://www.bioone.org/doi/abs/10.1667/0033-7587%282002%29158%5B0424%3ATSGBAC%5D2.0.CO%3B2?prevSearch=chernobyl&searchHistoryKey=&queryHash=f7283fdb5d57d03bfdb1eb17f03c59a5

Children of Chernobyl Cleanup Workers do not Show Elevated Rates of Mutations in Minisatellite Alleles

Title: Children of Chernobyl Cleanup Workers do not Show Elevated Rates of Mutations in Minisatellite Alleles

Author: L. A. Livshits, S. G. Malyarchuk, E. M. Lukyanova, Y. G. Antipkin, L. P. Arabskaya, S. A. Kravchenko, G. H. Matsuka , E. Petit, F. Giraudeau, P. Gourmelon, G. Vergnaud , and B. Le Guen

Reference: Radiation Research 155(1):74-80. 2001

DOI: http://dx.doi.org/10.1667/0033-7587(2001)155[0074:COCCWD]2.0.CO;2

Keywords : children, cleanup workers, mutations, minisatellite

Abstract: The disaster at the Chernobyl Nuclear Power Plant in April 1986 was accompanied by the release of large amounts of radioisotopes, resulting in the contamination of extensive regions of the Ukraine, Byelorus and the Russian Federation. Cleanup workers (liquidators) and people living on land contaminated with radioactive materials were most exposed. To assess the genetic effects of exposure to ionizing radiation after the Chernobyl accident, we have measured the frequency of inherited mutant alleles at seven hypermutable minisatellite loci in 183 children born to Chernobyl cleanup workers (liquidators) and 163 children born to control families living in nonirradiated areas of the Ukraine. There was no significant difference in the frequency of inherited mutant alleles between the exposed and control groups. The exposed group was then divided into two subgroups according to the time at which the children were conceived with respect to the fathers’ work at the power plant. Eighty-eight children were conceived either while their fathers were working at the facility or up to 2 months later (Subgroup 1). The other 95 children were conceived at least 4 months after their fathers had stopped working at the Chernobyl site (Subgroup 2). The frequencies of mutant alleles were higher for the majority of loci (i.e. 1.44 times higher for CEB1) in Subgroup 1 than in Subgroup 2. This result, if confirmed, would reconcile the apparently conflicting results obtained in the chronically exposed Byelorus population and the Hiroshima-Nagasaki A-bomb survivors.

URLhttp://www.bioone.org/doi/abs/10.166/0033-7587%282001%29155%5B0074%3ACOCCWD%5D2.0.CO%3B2?prevSearch=chernobyl&searchHistoryKey=&queryHash=05c5bf600dfdc400aa01511958fb5e34

Transgenerational accumulation of radiation damage in small mammals chronically exposed to Chernobyl fallout

Title: Transgenerational accumulation of radiation damage in small mammals chronically exposed to Chernobyl fallout

Author: Nadezhda I. Ryabokon, R. I. Goncharova

Reference: Radiation and Environmental Biophysics, September 2006, Volume 45, Issue 3, pp 167-177

DOI: 10.1007/s00411-006-0054-3

Keywords : radiation, accumulation, mammals, Chernobyl fallout

Abstract: The purpose of this investigation has been the analysis of the long-term development of biological damage in natural populations of a model mammalian species, the bank vole (Clethrionomys glareolus, Schreber), which were chronically exposed to low doses of ionizing radiation over 22 animal generations within 10 years following the Chernobyl accident. The time course of the biological end-points (chromosome aberrations in bone marrow cells and embryonic lethality) was compared with the time course of the whole-body absorbed dose rate from external and internal exposure in the studied populations inhabiting monitoring sites in Belarus with different ground deposition of radionuclides. The yield of chromosome aberrations and, in lesser degree, embryonic lethality was associated with the radionuclide contamination of the monitoring areas in a dose-dependent manner. As a main feature of the long-term development of biological damage under low dose rate irradiation, permanently elevated levels of chromosome aberrations and an increasing frequency of embryonic lethality have developed over 22 animal generations. This contrasts with the assumption that the biological damage would gradually disappear since in the same period of time the whole-body absorbed dose rate decreased exponentially with a half-value time of about 2.5–3 years. Furthermore, gravid females were captured, and their offspring, born and grown up under contamination-free laboratory conditions, showed the same enhanced level of chromosome aberrations. Therefore the authors suggest that, along with the biological damage attributable to the individual exposure of each animal, the observed cellular and systemic effects reflect the transgenerational transmission and accumulation, via genetic and/or epigenetic pathways, of damage attributable to the chronic low-dose rate exposure of the preceding generations of animals. They also suggest that the level of the accumulated transmissible damage in the investigated populations will decrease in future due to the further recession of the chronic exposure and as a consequence of selection processes.

URLhttp://link.springer.com/article/10.1007%2Fs00411-006-0054-3

(日本語) チェルノブイリ事故後慢性持続性低線量電離放射線に曝露したウクライナの患者の腎明細胞癌における微小血管密度は高い

Title: Microvessel density is high in clear-cell renal cell carcinomas of Ukrainian patients exposed to chronic persistent low-dose ionizing radiation after the Chernobyl accident

Author: A. M. Romanenko, A. Ruiz-Saurí, L. Morell-Quadreny, G. Valencia, A. F. Vozianov, A. Llombart-Bosch

Reference: Virchows Archiv , June 2012, Volume 460, Issue 6, pp 611-619

DOI: 10.1007/s00428-012-1243-x

Keywords : Conventional renal cell carcinoma, Ionizing radiation, Angiogenesis, Microvessel density, CD31antibody

Abstract: During the 25-year period subsequent to the Chernobyl accident, the morbidity of malignant renal tumors in Ukraine has increased from 4.7 to 10.7 per 100,000 of the total population. Recent studies of our group have shown that increases in morbidity, aggressiveness, and proliferative activity of renal cell carcinomas (RCCs), especially clear-cell renal cell carcinoma (CCRCC), in Ukrainian patients continuously inhabiting the radio-contaminated areas could be explained by specific molecular changes influenced by the so-called “chronic persistent low-dose ionizing radiation” (CPLDIR) exposure. This study aimed to examine the role of angiogenesis in CCRCC carcinogenesis associated with CPLDIR in patients living more than 20 years in cesium 137 (137Cs) contaminated areas after the Chernobyl accident in Ukraine. Paraffin-embedded specimens of 106 CCRCs were studied: Control cases were 18 tumors from Spanish patients (group 1), 25 tumors from Ukrainian patients from so-called clean areas without known radio-contamination (group 2), and 63 tumors from Ukrainian patients from radio-contaminated areas (group 3).

URL:http://link.springer.com/article/10.1007/s00428-012-1243-x

Cytogenetic Effects of Radiation on Agricultural Plants Observed in the Chernobyl region during the First Years after the Accident

Title: Cytogenetic Effects of Radiation on Agricultural Plants Observed in the Chernobyl region during the First Years after the Accident

Author: Stanislav A. GERASKIN, Vladimir G. DIKAREV, Yevgenia Ya. ZYABLITSKAYA, Alla A. OUDALOVA and Yevgeniy V. SPIRIN

Reference: Всероссийский Научно-Исследовательский Институт Сельскохозяйственной Радиологии и Агроэкологии

Keywords: cytogenetic effects, radiation, agricultural plants, first years after the accident, Belarus

Abstract: The cytogenetic consequences of radioactive contamination by the fallout after the accident at the Chernobyl NPP in 1986 to agricultural crops have been studied.

URLhttp://www.rri.kyoto-u.ac.jp/NSRG/reports/kr79/kr79pdf/Geraskin.pdf

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