Variable sensitivity of chromosomes 2, 8 and 14 in human peripheral blood lymphocytes exposed to heavy ions

Purpose: To investigate by FISH the distribution of radiation-induced chromosomal aberrations in chromosomes 2, 8 and 14 of 6 donors. Methods: Irradiation of blood from 6 healthy donors (4 male and 2 female) was performed at the accelerators at the Joint Institute for Nuclear Research in Dubna (Russia). Whole blood samples were irradiation with 3 Gy of protons (Phasotron), 3 Gy of 12C-ions (Nuclotron), 4 Gy of 7Li-ions and 3Gy of 11B-ions (Cyclotron U400M). At the position of the samples the beams energy and LET values were following: protons 170 MeV/n and LET ≈ 0.5 keV/µm; 12C 480 MeV/n and LET = 10.6 keV/µm; 7Li 30 MeV/n and LET ≈ 20 keV/µm; 11B 32 MeV/n and LET ≈ 55 keV/µm. Chromosome aberrations were analyzed in prematurely condensed G2-cells harvested after 48 in culture using calyculin A. Chromosomes 2, 8 and 14 were painted in different colors and aberrations scored with the help of an image-analysis system. Results: Chromosome 2 was generally less sensitive than expected on the basis of its DNA content. A higher than expected frequency of exchanges was found in chromosome 8, however, variable results were obtained for stable and unstable aberrations. The translocation frequency was higher and dicentric frequency was lower then expected. Chromosome 14 revealed the opposite tendency: for stable exchanges we found a lower sensitivity whereas the frequency of unstable exchanges was higher then expected. Generally, chromosome 14 was found to be less radiosensitive than expected. Conclusion: Chromosome 2 appears to be less sensitive to protons as well as to heavy ions than chromosomes 8 and 14. This result is in line with recent results of a study on the sensitivity of chromosomes 2, 8 and 14 to gamma rays

CABAS: A freely available PC program for fitting calibration curves in chromosome aberration dosimetry

The aim of biological dosimetry is to estimate the dose and the associated uncertainty to which an accident victim was exposed. This process requires the use of the maximum-likelihood method for fitting a calibration curve, a procedure that is not implemented in most statistical computer programs. Several laboratories have produced their own programs, but these are frequently not user-friendly and not available to outside users. We developed a software for fitting a linear-quadratic dose-response relationship by the method of maximum-likelihood and for estimating a dose from the number of aberrations observed. The program called as CABAS consists of the main curve-fitting and dose estimating module and modules for calculating the dose in cases of partial body exposure, for estimating the minimum number of cells necessary to detect a given dose of radiation and for calculating the dose in the case of a protracted exposure. © The Author 2007. Published by Oxford University Press. All rights reserved

Time-course of aberrations and their distribution: impact of LET and track structure

The biological response to high linear energy transfer (LET) radiation differs considerably from that to low LET radiation and this has been attributed to differences in the spatial energy deposition of both radiation qualities. In the case of X-rays the energy is deposited uniformly within the cell nucleus and produces damages in a purely stochastic manner. In contrast, for particles the energy is deposited inhomogeneously along the ion trajectory and the local dose decays with the square radial distance from the center of the track. This nonuniformity affects the yield and the distribution of aberrations among cells. Moreover, after high LET exposure a relationship between the aberration yield and cell cycle delay was observed. In this study, we present a detailed analysis of the distribution of aberrations in human lymphocytes reaching mitosis at early and later times after low and high LET exposure. Aberration data were fit to stochastic distributions demonstrating that the delay is related to the number of particle traversals per cell nucleus. To further elucidate this relationship, we introduce a Monte Carlo phenomenological model which incorporates the number of particle hits per nucleus. This value was derived by fitting theoretical distributions to the experimental data. Additionally, the probability that a cell traversed by a particle reaches mitosis at a given time was calculated. The analysis of biological data and numerical simulations clearly show the impact of the track structure on the formation of chromosome aberrations and their distribution among cells

Radiation-induced changes in levels of selected proteins in peripheral blood serum of breast cancer patients as a potential triage biodosimeter for large-scale radiological emergencies

The threat of a large scale radiological emergency, where thousands of people may require fast biological dosimetry for the purpose of triage, makes it necessary to search for new, high throughput biological dosimeters. The authors tested an assay based on the quantitative analysis of selected proteins in peripheral blood serum. They were particularly interested in testing proteins that are specific to irradiation of skin, as these can be used in cases of partial body exposure. Candidate proteins were identified in an earlier study with mice, where skin of the animals was exposed to different doses of radiation and global expression of serum proteins was analyzed. Eight proteins were found, the expression of which showed a consistent dose-response relationship. Human analogues of these proteins were identified, and their expression was measured in peripheral blood serum of 16 breast cancer patients undergoing external beam radiotherapy. The proteins were Apolipoprotein E; Apolipoprotein H; Complement protein 7; Prothrombinase; Pantothenate Kinase 4; Alpha-2-macroglobulin; Fetuin B and Alpha-1-Anti-Chymotrypsin. Measurements were carried out in blood samples collected prior to exposure (control), on the day after one fraction (2 Gy), on the day after five fractions (10 Gy), on the day after 10 fractions (20 Gy), and 1 mo after 23-25 fractions (total dose of 46-50 Gy). Multivariate analysis was carried out, and a multinomial logistic regression model was built. The results. © 2014 Health Physics Society