Comparative analysis of the yields of dicentrics and chromosomal translocations.

PURPOSE: Chromosomal dicentrics and translocations are commonly employed as biomarkers to estimate radiation doses. The main goal of this article is to perform a comparative analysis of yields of both types of aberrations. The objective is to determine if there are relevant distinctions between both yields, allowing for a comprehensive assessment of their respective suitability and accuracy in the estimation of radiation doses. MATERIALS AND METHODS: The analysis involved data from a partial-radiation simulation study with the calibration data obtained through two scoring methods: conventional and PAINT modified. Subsequently, a Bayesian bivariate zero-inflated Poisson model was employed to compare the posterior marginal density of the mean of dicentrics and translocations and assess the differences between them. RESULTS: When employing the conventional method of scoring, the findings indicate that there is no notable disparity between the yield of observed translocations and dicentrics. However, when utilizing the PAINT modified method, a notable discrepancy is observed for higher doses, indicating a relevant difference in the mean number of the two types of aberrations. CONCLUSIONS: The choice of scoring method significantly influences the analysis of radiation-induced aberrations, especially when distinguishing between complex and simple chromosomal formations. Further research and analysis are necessary to gain a deeper understanding of the factors and mechanisms impacting the formation of dicentrics and translocations.

Radiation dose estimation with time-since-exposure uncertainty using the [Formula: see text]-H2AX biomarker.

To predict the health effects of accidental or therapeutic radiation exposure, one must estimate the radiation dose that person received. A well-known ionising radiation biomarker, phosphorylated [Formula: see text]-H2AX protein, is used to evaluate cell damage and is thus suitable for the dose estimation process. In this paper, we present new Bayesian methods that, in contrast to approaches where estimation is carried out at predetermined post-irradiation times, allow for uncertainty regarding the time since radiation exposure and, as a result, produce more precise results. We also use the Laplace approximation method, which drastically cuts down on the time needed to get results. Real data are used to illustrate the methods, and analyses indicate that the models might be a practical choice for the [Formula: see text]-H2AX biomarker dose estimation process.

Establishment and validation of surface model for biodosimetry based on γ-H2AX foci detection.

INTRODUCTION: In the event of a radiation accident detecting γ-H2AX foci is being accepted as fast method for triage and dose assessment. However, due to their disappearance kinetics, published calibrations have been constructed at specific post-irradiation times. OBJECTIVES: To develop a surface, or tridimensional, model to estimate doses at times not included in the calibration analysis, and to validate it. MATERIALS AND METHODS: Calibration data was obtained irradiating peripheral mononucleated cells from one donor with radiation doses ranging from 0 to 3 Gy, and γ -H2AX foci were detected microscopically using a semi-automatic method, at different post-irradiation times from 0.5 to 24 h. For validation, in addition to the above-mentioned donor, blood samples from another donor were also used. Validation was done within the range of doses and post-irradiation times used in the calibration. RESULTS: The calibration data clearly shows that at each analyzed time, the γ-H2AX foci frequency increases as dose increases, and for each dose this frequency decreases with post-irradiation time. The γ-H2AX foci nucleus distribution was clearly overdispersed, for this reason to obtain bidimensional and tridimensional dose-effect relationships no probability distribution was assumed, and linear and non-linear least squares weighted regression was used. In the two validation exercises for most evaluated samples, the 95% confidence limits of the estimated dose were between ±0.5 Gy of the real dose. No major differences were observed between donors. CONCLUSION: In case of a suspected overexposure to radiation, the surface model here presented allows a correct dose estimation using γ-H2AX foci as biomarker. The advantage of this surface model is that it can be used at any post-irradiation time, in our model between 0.5 and 24 h.

Comparative study of micronucleus assays and dicentric plus ring chromosomes for dose assessment in particular cases of partial-body exposure.

Purpose: The goal was to compare the micronucleus (MN) and dicentric plus ring chromosomes (D + R) assays for dose assessment in cases of partial body irradiations (PBI). Materials and methods: We constructed calibration curves for each assay at doses ranging from 0 to 5 Gy of X-rays at dose rate of 0.275 Gy/min. To simulate partial-body exposures, blood samples from two donors were irradiated with 0.5, 1, 2 and 4 Gy and the ratios of irradiated to unirradiated blood were 25, 50, and 100%. Different tests were used to confirm if all samples were overdispersed or zero-inflated and for partial-body dose assessment we used the Qdr, Dolphin and Bayesian model. Results: In our samples for D + R calibration curve, practically all doses agreed with Poisson assumption, but MN exhibited overdispersed and zero-inflated cellular distributions. The exact Poisson tests and zero-inflated tests demonstrate that virtually all samples of D + R from PBI simulation fit the Poisson distribution and were not zero-inflated, but the MN samples were also overdispersed and zero-inflated. In the partial-body estimation, when Qdr and Dolphin methods were used the D + R results were better than MN, but the doses estimation defined by the Bayesian methodology were more accurate than the classical methods. Conclusions: Dicentric chromosomes continue to prove to be the best biological marker for dose assessment. However exposure scenarios of partial-body estimation, overdispersion and zero-inflation may not occur, it being a critical point not only for dose assessment, but also to confirm partial-body exposure. MN could be used as alternative assay for partial-body dose estimation, but in case of an accident without any information, the MN assay could not define whether the accident was a whole-body irradiation (WBI) or a PBI.

In vitro cytogenetic and genotoxic effects of curcumin on human peripheral blood lymphocytes.

Curcumin has shown a wide range of properties such as anti-inflammatory and anti-carcinogenic properties. Many of these effects, mainly the anti-carcinogenic effect, could be linked to its anti-oxidant effects. Nevertheless, some studies suggest that this natural compound possesses both pro- and anti-oxidative effects and that curcumin could be a genotoxic agent for some cell lines. We evaluated the genetic damage induced by curcumin to human lymphocytes exposed to increasing concentrations (0-50 µg/ml) of curcumin. Biomarkers such as chromosome aberrations (CAs) and sister chromatid exchange (SCE) were analyzed. In addition to the cytogenetic analysis, the effect of curcumin in the cell proliferation kinetics (CPK) by the proliferation index (PI) was also analyzed. The results indicated that high concentrations of curcumin induced CAs, mainly acentric fragments. SCEs rate was not statistically different from the control group in any curcumin treated cell group. The PI of cells treated with 2 and 5 µg/ml of curcumin were statistically significant from the control group and finally, the MI showed a tendency to increase in all the concentrations of curcumin tested. In conclusion, it can be assumed that the higher concentrations of curcumin evaluated have a cyto and genotoxic effect, in vitro, for human peripheral lymphocytes.

International study of factors affecting human chromosome translocations.

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 16 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 versus 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.