Three somatic genetic biomarkers and covariates in radiation-exposed Russian cleanup workers of the chernobyl nuclear reactor 6-13 years after exposure.

Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, California 94550, USA.
Radiation Research (Impact Factor: 2.91). 11/2002; 158(4):424-42.
Source: PubMed


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.

27 Reads
  • Source
    • "[1–5] which have been the gold standard for many years but these assays are costly and can take weeks to conduct. Gene mutation assays such as HPRT [1,6,7] and Glycophorin A [1,6,8,9] have also been used, although these are not usually as accurate as cytogenetics [1] and only work on individuals of the appropriate genotype or gender. Electron paramagnetic resonance has also been used successfully [9]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Rapid and reliable methods for performing biological dosimetry are of paramount importance in the event of a large-scale nuclear event. Traditional dosimetry approaches lack the requisite rapid assessment capability, ease of use, portability and low cost, which are factors needed for triaging a large number of victims. Here we describe the results of experiments in which mice were acutely exposed to (60)Co gamma rays at doses of 0 (control) to 10 Gy. Blood was obtained from irradiated mice 0.5, 1, 2, 3, 5, and 7 days after exposure. mRNA expression levels of 106 selected genes were obtained by reverse-transcription real time PCR. Stepwise regression of dose received against individual gene transcript expression levels provided optimal dosimetry at each time point. The results indicate that only 4-7 different gene transcripts are needed to explain ≥ 0.69 of the variance (R(2)), and that receiver-operator characteristics, a measure of sensitivity and specificity, of ≥ 0.93 for these statistical models were achieved at each time point. These models provide an excellent description of the relationship between the actual and predicted doses up to 6 Gy. At doses of 8 and 10 Gy there appears to be saturation of the radiation-response signals with a corresponding diminution of accuracy. These results suggest that similar analyses in humans may be advantageous for use in a field-portable device designed to assess exposures in mass casualty situations.
    PLoS ONE 12/2013; 8(12):e83390. DOI:10.1371/journal.pone.0083390 · 3.23 Impact Factor
  • Source
    • "XMEs) on chromosome aberration frequencies in healthy populations [14] [15] and see [16] for a review. Translocation frequencies in peripheral blood lymphocytes are the most appropriate measure of chromosome aberrations for assessing chronic and historical exposure to radiation [17] since cells containing translocations are stable and are able to pass through repeated cell divisions. Translocation frequencies thus provide an integrated measure of a lifetime's exposure to clastogenic agents. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Polymorphic variation in DNA repair genes was examined in a group of retired workers from the British Nuclear Fuels plc facility at Sellafield in relation to previously determined translocation frequencies in peripheral blood lymphocytes. Variation at seven polymorphisms in four genes involved in the base excision repair (XRCC1 R194W, R399Q and a [AC]n microsatellite in the 3' UTR) and double strand break repair (XRCC3 T241M and a [AC]n microsatellite in intron 3 of XRCC3, XRCC4 I134T, and a GACTAn microsatellite located 120 kb 5' of XRCC5) pathways was determined for 291 retired radiation workers who had received cumulative occupational external radiation doses of between 0 and 1873 mSv. When the interaction between radiation dose and each DNA repair gene polymorphism was examined in relation to translocation frequency there was no evidence for any of the polymorphisms studied influencing the response to occupational exposure. A positive interaction observed between genotype (individuals with at least one allele > or =20 repeat units) at a microsatellite locus in the XRCC3 gene and smoking status should be interpreted cautiously because interactions were investigated for seven polymorphisms and two exposures. Nonetheless, further research is warranted to examine whether this DNA repair gene variant might be associated with a sub-optimal repair response to smoking-induced DNA damage and hence an increased frequency of translocations.
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 03/2005; 570(1):137-45. DOI:10.1016/j.mrfmmm.2004.11.002 · 3.68 Impact Factor
  • Source
    • " the HPRT locus are more indirect measures of exposure , but have the potential to be integrating measures of exposure over time and may be more closely related to the biological events leading to tumorogenesis . Again large differences in response are noted among individuals with similar exposures ( Bigbee et al . , 1998 ; Thomas et al . , 1999 ; Jones et al . , 2002 ) . Genetic differences in the ability of cells to metabolically by guest on May 23 , 2011 tpx . sagepub . com Downloaded from Vol . 32 ( Suppl . 1 ) , 2004 GENETIC VARIATION AND RISK ESTIMATION 141 activate and / or detoxify mutagenic agents explain some of the variation observed among individuals with similar ex - posures ( Lutz , 199"
    [Show abstract] [Hide abstract]
    ABSTRACT: With the vast technological and informational resources increasingly available from investments in "genomics," toxicology and much of biological science, is faced with previously undreamed of opportunities and equally daunting challenges. The ability to generate the large quantities of data becoming routinely available could not be imagined a decade ago. The complexities of data analysis are increasingly the rate-limiting element in scientific advances. The expectations that these large scientific investments will reduce the incidence of human disease and improve health are very high. An emphasis on genetic variation and Toxicogenetics is expected to yield risk estimates for specific rather than average individuals and individuals with varied lifestyles and complex patterns of exposure. Examples from studies of polymorphic variation in DNA repair genes in the healthy population and cancer risk highlight the complexity and challenges of incorporating genetic variation into quantitative estimates of risk associated with environmentally relevant exposures. Similar issues exist in selecting the animal models most appropriate for predicting human risk from environmental exposures to toxic agents.
    Toxicologic Pathology 03/2004; 32 Suppl 1(Suppl 1):136-45. DOI:10.1080/01926230490424671 · 2.14 Impact Factor
Show more


27 Reads
Available from