Current status of biodosimetry based on standard cytogenetic methods

Abstract

Knowledge about dose levels in radiation protection is an important step for risk assessment. However, in most cases of real or suspected accidental exposures to ionizing radiation (IR), physical dosimetry cannot be performed for retrospective estimates. In such situations, biological dosimetry has been proposed as an alternative for investigation. Briefly, biodosimetry can be defined as individual dose evaluation based on biological endpoints induced by IR (so-called biomarkers). The relationship between biological endpoints and absorbed dose is not always straightforward: nausea, vomiting and diarrhoea, for example, are the most well-known biological effects of individual irradiation, but a precise correlation between those symptoms and absorbed dose is hardly achieved. The scoring of unstable chromosomal-type aberrations (such as dicentrics and rings) and micronuclei in mitogen-stimulated peripheral blood, up till today, has been the most extensively biodosimetry assay employed for such purposes. Dicentric assay is the gold standard in biodosimetry, since its presence is generally considered to be specific to radiation exposure; scoring of micronuclei (a kind of by-product of chromosomal damages) is easier and faster than that of dicentrics for dose assessment. In this context, the aim of this work is to present an overview on biodosimetry based on standard cytogenetic methods, highlighting its advantages and limitations as tool in monitoring of radiation workers' doses or investigation into accidental exposures. Recent advances and perspectives are also briefly presented.

Use of the γ-H2AX assay to monitor DNA damage and repair in translational cancer research

“…Over the past decades, the most commonly used method in biological dosimetry was cytogenetic analysis, in which the stable (translocations) and unstable (dysenteric chromosomes, micronuclei) chromosomal aberrations are counted in peripheral blood lymphocytes, along with a few other methods such as the glycophorin A mutation assay, electron paramagnetic resonance in tooth enamel, and the comet assay [69; 70]. However, cytogenetic analysis is time-consuming; it implies growth stimulation for 48–72 hrs since chromosomal damage can only be measured in metaphases [71]. Thus, such an analysis is not suitable for the rapid identification of the most severely exposed individuals, which is required in the event of a large-scale radiation emergency, when reliable detection is needed for population triage during the first few hours after accidental radiation exposure.…”

Implementation of a dose–response curve for γ-radiation in the Portuguese population by use of the chromosomal aberration assay

“…Dose-response curves have shapes and slopes that differ as a function of LET and relative biological effectiveness [17]. For low-LET radiation (e.g.…”

“…According to the IAEA [11], each laboratory must have its own dose-response curve, since several factors can influence the dose-effect relationships such as culture conditions or dicentric scoring efficiency [2,3,[12][13][14][15][16]. The main advantages of scoring dicentrics is its high specificity for ionizing radiation, low background in non-exposed populations (about 1 dicentric per 1000 cells) and a low detection limit, about 0.1 Gy for low-LET radiation if 500-1000 metaphases are scored [6,11,17,18]. Studies on both lowand high-LET radiation demonstrated that exposures in vitro and in vivo produce similar yields of dicentrics per unit dose [6,12,16].…”

Microfluidics as a new tool in radiation biology

“…Cytogenetic assays are the most extensively used biodosimetry assays, such as premature chromosome condensation (PCC) assay, micronuclei formation scoring, translocation and dicentric assay together [48]. Dicentric assay is currently the gold standard dosimetric method.…”