Study of the tools available in biological dosimetry to estimate the dose in cases of accidental complex overexposure to ionizing radiation: The Lilo accident

Roy, Laurence; Grégoire, Éric; Durand, Valérie; Buard, Valérie; Delbos, M; Paillole, N.; Sorokine-Durm, I.; Gourmelon, P.; Voisin, Philippe

doi:10.1080/09553000600579207

Cited by 30 publications

(12 citation statements)

References 21 publications

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“…One particular aberration, a chromosomal translocation, appears so frequently that it can be used for dosimety purposes [65,66] and can be stable for months after the initial exposure [67]. Due to the overwhelming evidence that chromosomal translocations are a major component of the genome instability that promotes cellular dysregulation in many types of leukemias and lymphomas [20,68], it is clear that understanding how translocations form following irradiation is of paramount importance.…”

Section: Discussionmentioning

confidence: 99%

RAD59 is required for efficient repair of simultaneous double-strand breaks resulting in translocations in Saccharomyces cerevisiae

2008

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Exposure to ionizing radiation results in a variety of genome rearrangements that have been linked to tumor formation. Many of these rearrangements are thought to arise from the repair of doublestrand breaks (DSBs) by several mechanisms, including homologous recombination (HR) between repetitive sequences dispersed throughout the genome. Doses of radiation sufficient to create DSBs in or near multiple repetitive elements simultaneously could initiate single-strand annealing (SSA), a highly-efficient, though mutagenic, mode of DSB repair. We have investigated the genetic control of the formation of translocations that occur spontaneously and those that form after the generation of DSBs adjacent to homologous sequences on two, non-homologous chromosomes in Saccharomyces cerevisiae. We found that mutations in a variety of DNA repair genes have distinct effects on break-stimulated translocation. Furthermore, the genetic requirements for repair using 300 bp and 60 bp recombination substrates were different, suggesting that the SSA apparatus may be altered in response to changing substrate lengths. Notably, RAD59 was found to play a particularly significant role in recombination between the short substrates that was partially independent of that of RAD52. The high frequency of these events suggests that SSA may be an important mechanism of genome rearrangement following acute radiation exposure.

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Section: Discussionmentioning

confidence: 99%

RAD59 is required for efficient repair of simultaneous double-strand breaks resulting in translocations in Saccharomyces cerevisiae

2008

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“…The fraction of exchanges detected was calculated using equations appropriate for one-to three-color paints [31] and was based on the DNA content of the painted chromosomes [32]. The proportion of genome coverage differs slightly for males and females due to the larger size of the X compared to the Y chromosome and some laboratories adjust for these gender differences in their calculations.…”

Section: Discussionmentioning

confidence: 99%

“…Individual laboratories cultured the blood samples and painted various combinations of chromosomes according to their routine practices [10,15,[27][28][29][30][31][32][33][34][35]. The specific chromosomes that were painted and the number of colors used by each laboratory are shown in Table 1.…”

Section: Blood Sample Collection and Culture Methodsmentioning

confidence: 99%

International study of factors affecting human chromosome translocations

Sigurdson

Hauptmann

et al. 2008

Mutation Research/Genetic Toxicology and Environmental Mutagene

122

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Abstract*Correspondence, page proofs, and reprint requests to: James D. Tucker, Ph.D., Department of Biological Sciences, 1370 Biological Sciences Building, 5047 Gullen Mall, Wayne State University, Detroit, TEL: (313) 577-2783, FAX: (313) 577-3602, EMAIL: E-mail: jtucker@biology.biosci.wayne.edu. z Retired Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Chromosome translocations in peripheral blood lymphocytes of normal, healthy humans increase with age, but the effects of gender, race, and cigarette smoking on background translocation yields have not been examined systematically. Further, the shape of the relationship between age and translocation frequency (TF) has not been definitively determined. We collected existing data from sixteen laboratories in North America, Europe, and Asia on TFs measured in peripheral blood lymphocytes by fluorescence in situ hybridization whole chromosome painting among 1933 individuals. In Poisson regression models, age, ranging from newborns (cord blood) to 85 years, was strongly associated with TF and this relationship showed significant upward curvature at older ages vs. a linear relationship (p <0.001). Ever smokers had significantly higher TFs than non-smokers (rate ratio (RR) = 1.19, 95% confidence interval (CI), 1.09-1.30) and smoking modified the effect of age on TFs with a steeper age-related increase among ever smokers compared to non-smokers (p<0.001). TFs did not differ by gender. Interpreting an independent effect of race was difficult owing to laboratory variation. Our study is three times larger than any pooled effort to date, confirming a suspected curvilinear relationship of TF with age. The significant effect of cigarette smoking has not been observed with previous pooled studies of TF in humans. Our data provide stable estimates of background TF by age, gender, race, and smoking status and suggest an acceleration of chromosome damage above age 60 and among those with a history of smoking cigarettes. NIH Public Access

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“…Both models have been validated in vitro by mixing irradiated and unirradiated blood in different proportions [5]. These approaches have also been tested in vivo in accidental situations, with promising results [6,7]. Furthermore, recent in vivo studies of cancer patients who had received 8 Gy of radiotherapy in a single fraction have shown that the derived partial-body dose obtained with both Qdr and Dolphin methods are in agreement with the doses estimated from the radiotherapy regimens [8].…”

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confidence: 50%

Cytogenetic assessment of heterogeneous radiation doses in cancer patients treated with fractionated radiotherapy

Roch-Lefèvre

Pouzoulet²,

Giraudet³

et al. 2010

BJR

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ABSTRACT. The purpose of this study was to evaluate the in vivo dose-response relation of chromosome aberration formation and distribution in a context of localised and fractionated radiotherapy. Cytogenetic analysis was applied to eight patients, all treated for the same tumour localisation; the same localisation was used to prevent the variability usually observed between patients treated with radiotherapy and to allow the corresponding roles of the size of irradiation field and of the dose rate to be studied. The yield of dicentrics, centric rings and fragments was measured in blood samples taken before treatment, during the course of radiotherapy and up to 6 months after. After the first fraction of radiotherapy, we observed that the whole-body dose estimated from the yield of dicentrics and rings was higher (0.35¡0.2 Gy) than the calculated equivalent whole-body dose (0.07¡0.04 Gy). By contrast, the partial-body dose derived from the Qdr (quotient of dicentrics and rings) model was estimated to be 2.2¡0.3 Gy, which agreed quite well with the dose delivered to the tumour (2.1¡0.1 Gy). We also found a correlation between the yield of induced chromosome aberrations and the target field size (p50.014). U-value analysis showed that the distribution of dicentrics and rings was overdispersed, despite the fractionation of the exposure, and a positive correlation between the U-value and the dose rate was observed (p50.017). Overall, these results suggest that the proportion of undamaged lymphocytes could increase with the dose rate.

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Study of the tools available in biological dosimetry to estimate the dose in cases of accidental complex overexposure to ionizing radiation: The Lilo accident

Abstract: It has been useful to compare cytogenetic results with clinical results. The results presented here reveal good stability of translocations. However the first dose estimation was not attempted until 6 months after the last exposure.

Cited by 30 publications

References 21 publications

RAD59 is required for efficient repair of simultaneous double-strand breaks resulting in translocations in Saccharomyces cerevisiae

RAD59 is required for efficient repair of simultaneous double-strand breaks resulting in translocations in Saccharomyces cerevisiae

International study of factors affecting human chromosome translocations

Cytogenetic assessment of heterogeneous radiation doses in cancer patients treated with fractionated radiotherapy

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