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General Radiation Cytopathology
Published in George W. Casarett, Radiation Histopathology, 2019
In unstable aberrations of the chromosomes, material may be lost from the genomes during division, so that nonviable daughter cells are generally produced, eventually leading to death of the cell line. The loss occurs when acentric pieces fail to attach to the mitotic spindle and when anaphase bridges are formed from dicentric aberrations. This type of aberration, being relatively easy to observe at metaphase, is particularly valuable in scoring for radiation dosimetry. They are usually classified into three types: Dicentric plus a fragment, which involves a break in each of two chromosomes which wrongly rejoin to form a structure with two centromeres plus an acentric fragment.Centric ring plus a fragment, which involves two breaks in the same chromosome, on either side of the centromere, which rejoin wrongly to form a ring including the centromere, with an acentric fragment remaining.Acentrics and terminal deletions, interstitial deletions, and acentric rings.
Cell death after irradiation: How, when and why cells die
Published in Michael C. Joiner, Albert J. van der Kogel, Basic Clinical Radiobiology, 2018
Why does irradiation cause proliferating cells to undergo mitotic catastrophe and cell death? This appears to result from the fact that although DDR pathways remove much of the initial damage caused by irradiation, they are unable to prevent some cells with DNA breaks or DNA rearrangements from entering mitosis. The consequences of incomplete or improper DNA repair become readily visible as chromosomes condense in metaphase as a series of different types of chromosome aberrations. The fate of cells harbouring chromosome aberrations is largely determined by the nature of the chromosome aberration itself (Figure 3.3) (1). Studies have demonstrated approximately equal numbers of reciprocal translocations and non-reciprocal translocations (a dicentric chromosome + acentric fragment) are formed after irradiation. Both of these types of aberrations result from misrepair in which chromosome ends are incorrectly ligated together in a largely stochastic process. However, whereas cells with dicentrics and acentric fragments all die, those with reciprocal translocations often survive. The presence of two centromeres in dicentric chromosomes prevents their separation at metaphase, and consequently leads to mitotic catastrophe and eventually cell death. Some cells with dicentric chromosomes may manage to complete mitosis, however, loss of genetic material present in the acentric fragment (which forms a ‘micronuclei’) in subsequent mitosis may lead to subsequent death at a later time. This explains the good correlation which has been observed between the formation of dicentric chromosomes or micronuclei formation and cell survival. Reciprocal translocations do not cause problems at metaphase, and thus do not cause mitotic catastrophe or cell death. In fact, these types of aberrations can be found in cells from people exposed to irradiation many years later.
Quantitative relationships between acentric fragments and micronuclei: new models and implications for curve fitting
Published in International Journal of Radiation Biology, 2020
The first study on the kinetics of AFs was made by Sasaki and Norman (1967) measuring their frequencies at the first, second, and third post-irradiation mitoses, concluding that an AF has a 30% probability to arrive to the next mitosis. Correcting these calculations with the effect on cell proliferation, Carrano and Heddle (1973) gave a new estimation of 80%. The main obstacle in these early studies is that cells are not synchronized: “first mitosis” in reality includes cells that are already going through the second one. This issue was later corrected with the BrdU-Giemsa technique, giving unequivocal identification of metaphases at different divisions. Das and Sharma (1987) found that in Muntjac cells the frequencies of AFs per post-irradiated first, second and third division were 2.21, 0.64 and 0.24, respectively; that is, between the first and second mitoses 71% AFs are lost and 63% between the second and third one. Bauchinger et al. (1986) determined the probability that a dicentric survives (i.e. does not form an anaphase bridge) and arrives at the next mitosis as 0.45 and that the probability that an AF is lost decreases with dose, from 0.24 to 0.02. However, the formulas they employed (Braselmann et al. 1986) did not consider the possibility that a dicentric goes in a daughter cell and the accompanying acentric fragment (aAF) in the other one.
Induction of chromosomal aberrations and micronuclei by 2-hydroxy-4-methoxybenzophenone (oxybenzone) in human lymphocytes
Published in Drug and Chemical Toxicology, 2019
Alfredo Santovito, Stefano Ruberto, Gabriella Galli, Costanza Menghi, Marilena Girotti, Piero Cervella
With regard to the opportunity to include gaps in the statistical analyses, the discussion is open. Although some authors considered gaps as the appropriate indicator of genotoxic potential of chemicals (Savage 2004), the molecular mechanism of BP-3 to induce achromatic lesion/gaps is yet to be revealed. Thus, in our statistical analyses, we decided to exclude gaps. The criteria for distinguishing chromatide breaks from gaps were the acentric piece displaced with respect to the chromosome axis and the size of the discontinuity, which exceeded the width of the chromatide. A dicentric with an acentric fragment was scored as one aberration.
Comparative study of micronucleus assays and dicentric plus ring chromosomes for dose assessment in particular cases of partial-body exposure
Published in International Journal of Radiation Biology, 2019
Mariana E. Mendes, Julyanne C. G. Mendonça, Joan F. Barquinero, Manuel Higueras, Jorge E. Gonzalez, Aida M. G. Andrade, Laís M. Silva, Alyne M. S. Nascimento, Julianne C. F. Lima, Júlio C. G. Silva, Suy Hwang, Ana M. M. A. Melo, Neide Santos, Fabiana F. Lima
For the construction of calibration curve, at least 1000 complete metaphases or until 100 dicentrics plus ring chromosomes (D + R) in each sample were counted. For partial-body estimations 500 cells or 100 D + R were counted to give a reasonably accurate estimate of dose (IAEA 2011). Following IAEA recommendations dicentrics or rings were only considered if an accompanying acentric fragment was present, acentric fragments not related to dicentrics or rings were considered as excess acentrics fragments (Ace).