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

Jones, Irene M.; Galick, Heather; Kato, Paula; Langlois, Richard G.; Mendelsohn, Mortimer L.; Murphy, Gloria A.; Pleshanov, Pavel; Ramsey, Marilyn J.; Thomas, C.; Tucker, James D.; Tureva, Ludmila; Vorobtsova, I.E.; Nelson, David

doi:10.1667/0033-7587(2002)158[0424:tsgbac]2.0.co;2

Cited by 63 publications

(33 citation statements)

References 64 publications

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“…Advances in the application of genetic methodologies will no doubt continue to identify new genetic variants with small independent effects, but a knowledge of both polygenic effects and complex interactions may be required to fully understand disease causation (2). In some cases, specific environmental exposures are associated with increasing mutation rate, with a dose-dependent increase in genetic damage and disease risk (9)(10)(11)(12).…”

mentioning

confidence: 99%

Prospects for Epigenetic Epidemiology

Foley¹,

Craig²,

Morley³

et al. 2008

American Journal of Epidemiology

215

162

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mentioning

confidence: 99%

Prospects for Epigenetic Epidemiology

Foley¹,

Craig²,

Morley³

et al. 2008

American Journal of Epidemiology

215

162

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“…Chromosomal translocations, a recognized and validated biomarker of exposure to ionizing radiation (31), have been measured previously in these individuals (32). When translocation frequencies are compared between these same individuals, there is a statistically significant difference that is attributable to radiation exposure (control group translocation frequency ϭ 17.41 Ϯ 2.25 ϫ 10 Ϫ3 per genome equivalent; exposed group translocation frequency ϭ 28.41 Ϯ 2.87 ϫ 10 Ϫ3 per genome equivalent; P ϭ 0.041).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA Mutations in Individuals Occupationally Exposed to Ionizing Radiation

Wilding¹,

Cadwell²,

Tawn³

et al. 2006

Radiation Research

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Mutations in a 443-bp amplicon of the hypervariable region HVR1 of the D-loop of mitochondrial DNA (mtDNA) were quantified in DNA extracted from peripheral blood samples of 10 retired radiation workers who had accumulated external radiation doses of Ͼ0.9 Sv over the course of their working life and were compared to the levels of mutations in 10 control individuals matched for age and smoking status. The mutation rate in the 10 exposed individuals was 9.92 ؋ 10 Ϫ5 mutations/ nucleotide, and for the controls it was 8.65 ؋ 10 Ϫ5 mutations/ nucleotide, with a procedural error rate of 2.65 ؋ 10 Ϫ5 mutations/nucleotide. No increase in mtDNA mutations due to radiation exposure was detectable (P ‫؍‬ 0.640). In contrast, chromosomal translocation frequencies, a validated radiobiological technique for retrospective dosimetric purposes, were significantly elevated in the exposed individuals. This suggests that mutations identified through sequencing of mtDNA in peripheral blood lymphocytes do not represent a promising genetic marker of DNA damage after low-dose or low-doserate exposures to ionizing radiation. There was an increase in singleton mutations above that attributable to procedural error in both exposed and control groups that is likely to reflect age-related somatic mutation. ᭧

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“…Jones and co-workers [28] reported on application of three somatic genetic biomarkers [translocations by FISH, hypoxanthine phosphoribosyltransferase (HPRT) mutant frequency by cloning and for glycophorin A (GPA) by flow cytometry] and covariates in radiation exposed Russian cleanup workers (625) of the Chernobyl nuclear reactor 6-13 years after exposure. The results revealed higher frequency of translocations and HPRT but not for GPA.…”

Section: Chernobyl Experiences On Genomic Instabilitymentioning

confidence: 99%

Cytogenetic Biological Dosimetry Past, Present and Future Perspectives

Darroudi

2012

Sixth International Conference on Environmental Mutagens in Human Populations

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Abstract. Human risk assessments at the low doses, and low dose rates and high doses following acute exposure to ionizing radiation are of prime importance in radiation protection. These issues are of continuing importance in respect of social/economic policy relating to the industrial and medical uses of ionizing radiation, and for risk assessment among people occupationally are being exposed to low and/or high LET radiation, such as astronauts, pilots, stewardess and nuclear power plant workers, as well as victims of radiation accidents. Consequently, several biological assays were developed and attempts were made to investigate formation of radiation induced chromosome aberrations and induction of genomic instability in human lymphocytes and fibroblasts. Fluorescence in situ hybridization (FISH) technique using chromosome, chromosome-arm, chromosome region, centromere and telomere specific DNA libraries has improved the resolution of detecting all classes of radiation induced chromosomal inter-and intra-changes. Consequently, has increased significantly the accuracy and detection limit of biological dosimetry. Newly obtained data indicate that (a) Premature chromosome condensation assay is a unique method to be used for immediate dose assessment at low (5cGy) as well as high doses (≥3 Gy) and can accurately discriminate between whole-and partial-body exposure in case of mass casualties and accidental over-exposure to high doses of ionizing radiation (b) FISH-based translocation assay has the potential to assess acute as well as chronic exposure in cases of accidental as well as occupational exposure to ionizing radiation, either immediately following exposure, or retrospectively by defining accumulative effects to red bone marrows. (c) there are distinct finger-prints (such as insertions and complex translocations) for high LET radiation in comparison to low LET radiation. The importance of these findings and future perspectives for biological dosimetry are discussed.

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

Cited by 63 publications

References 64 publications

Prospects for Epigenetic Epidemiology

Prospects for Epigenetic Epidemiology

Mitochondrial DNA Mutations in Individuals Occupationally Exposed to Ionizing Radiation

Cytogenetic Biological Dosimetry Past, Present and Future Perspectives

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