Chromosome translocations and assessing human exposure to adverse environmental agents

Tucker, James D.

doi:10.1002/em.20561

Cited by 18 publications

(9 citation statements)

References 82 publications

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“…In both studies the number of metaphase cells counted was converted to whole genome cell equivalents, as if the full genome had been scored (40). The conversion to whole genome equivalent is performed using the formula derived by Lucas et al (41), i.e., F p = 2.05 f p (1 – f p ) F G where F p is the measured frequency of translocations detected by FISH, f p is the painted fraction of the genome and F G is the (true) genomic aberration frequency.…”

Section: Methodsmentioning

confidence: 99%

Association of Chromosome Translocation Rate with Low Dose Occupational Radiation Exposures in U.S. Radiologic Technologists

et al. 2014

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Chromosome translocations are a well-recognized biological marker of radiation exposure and cancer risk. However, there is uncertainty about the lowest dose at which excess translocations can be detected, and whether there is temporal decay of induced translocations in radiation-exposed populations. Dosimetric uncertainties can substantially alter the shape of dose-response relationships; although regression-calibration methods have been used in some datasets, these have not been applied in radio-occupational studies, where there are also complex patterns of shared and unshared errors that these methods do not account for. In this article we evaluated the relationship between estimated occupational ionizing radiation doses and chromosome translocation rates using fluorescent in situ hybridization in 238 U.S. radiologic technologists selected from a large cohort. Estimated cumulative red bone marrow doses (mean 29.3 mGy, range 0–135.7 mGy) were based on available badge–dose measurement data and on questionnaire-reported work history factors. Dosimetric assessment uncertainties were evaluated using regression calibration, Bayesian and Monte Carlo maximum likelihood methods, taking account of shared and unshared error and adjusted for overdispersion. There was a significant dose response for estimated occupational radiation exposure, adjusted for questionnaire-based personal diagnostic radiation, age, sex and study group (5.7 translocations per 100 whole genome cell equivalents per Gy, 95% CI 0.2, 11.3, P = 0.0440). A significant increasing trend with dose continued to be observed for individuals with estimated doses <100 mGy. For combined estimated occupational and personal-diagnostic-medical radiation exposures, there was a borderline-significant modifying effect of age (P 0.0704), but little evidence (P > 0.5) of temporal decay of induced translocations. The three methods of analysis to adjust for dose uncertainty gave similar results. In summary, chromosome translocation dose-response slopes were detectable down to <100 mGy and were compatible with those observed in other radiation-exposed populations. However, there are substantial uncertainties in both occupational and other (personal-diagnostic-medical) doses that may be imperfectly taken into account in our analysis.

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Section: Methodsmentioning

confidence: 99%

Association of Chromosome Translocation Rate with Low Dose Occupational Radiation Exposures in U.S. Radiologic Technologists

et al. 2014

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“…[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.…”

Section: Introductionmentioning

confidence: 99%

Gene Expression-Based Dosimetry by Dose and Time in Mice Following Acute Radiation Exposure

et al. 2013

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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 60Co 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 (R2), 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.

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“…Tucker has described in detail the calculations for the fraction of the genome covered and how to determine the fraction of detectable exchanges using two color combinations of painted chromosomes (and the counterstain) [ 8 ].…”

Section: Notementioning

confidence: 99%

“…Furthermore, chromosome size is important, as larger chromosomes are more likely to be involved in rearrangements than smaller chromosomes. The mathematical relationship between the number of chromosomes painted, the size of those chromosomes, and the number of colors used has been described in detail [ 8 ]. The terms "cell equivalents" or "whole genome equivalents" are used to relate the number of metaphase cells scored to the corresponding number of whole genomes evaluated.…”

Section: Introductionmentioning

confidence: 99%

Chromosome Painting of Mouse Peripheral Blood and Spleen Tissues

Petibone

Tucker

Morris

2014

Genotoxicity and DNA Repair

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Exposure to genotoxins may induce both structural and numerical chromosome aberrations. Whole chromosome fl uorescence in situ hybridization (FISH) of metaphase cells provides a means for analyzing chromosome aberrations with single-cell level resolution. The laboratory mouse model is an essential tool for in vivo genotoxicity studies. However, few published resources are available that provide a comprehensive background and instructions on how to perform whole chromosome FISH on mouse metaphase cells. Here, we consolidate several techniques into a single, comprehensive protocol describing the preparation of mouse metaphase cells for whole chromosome FISH analysis. Also presented are basic recommendations on how to visualize the slides and how to organize the data for analysis and interpretation.

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Chromosome translocations and assessing human exposure to adverse environmental agents

Cited by 18 publications

References 82 publications

Association of Chromosome Translocation Rate with Low Dose Occupational Radiation Exposures in U.S. Radiologic Technologists

Association of Chromosome Translocation Rate with Low Dose Occupational Radiation Exposures in U.S. Radiologic Technologists

Gene Expression-Based Dosimetry by Dose and Time in Mice Following Acute Radiation Exposure

Chromosome Painting of Mouse Peripheral Blood and Spleen Tissues

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