High Resolution and Automatable Cytogenetic Biodosimetry Using In Situ Telomere and Centromere Hybridization for the Accurate Detection of DNA Damage: An Overview

Abstract

In the event of a radiological or nuclear accident, or when physical dosimetry is not available, the scoring of radiation-induced chromosomal aberrations in lymphocytes constitutes an essential tool for the estimation of the absorbed dose of the exposed individual and for effective triage. Cytogenetic biodosimetry employs different cytogenetic assays including the scoring of dicentrics, micronuclei, and translocations as well as analyses of induced premature chromosome condensation to define the frequency of chromosome aberrations. However, inherent challenges using these techniques include the considerable time span from sampling to result, the sensitivity and specificity of the various techniques, and the requirement of highly skilled personnel. Thus, techniques that obviate these challenges are needed. The introduction of telomere and centromere (TC) staining have successfully met these challenges and, in addition, greatly improved the efficiency of cytogenetic biodosimetry through the development of automated approaches, thus reducing the need for specialized personnel. Here, we review the role of the various cytogenetic dosimeters and their recent improvements in the management of populations exposed to genotoxic agents such as ionizing radiation. Finally, we discuss the emerging potentials to exploit these techniques in a wider spectrum of medical and biological applications, e.g., in cancer biology to identify prognostic biomarkers for the optimal triage and treatment of patients.

Applicability of Scoring Calyculin A-Induced Premature Chromosome Condensation Objects for Dose Assessment Including for Radiotherapy Patients

“…As a well-established method in biodosimetry, DCA is more accurate for doses below 2 Gy than the calyculin A-induced PCC. PCC is therefore not preferred for this dose range, but rather it is suggested as an alternative method, especially when it is difficult to obtain sufficient number of cells to score for the elderly and those with pathological conditions [Gotoh and Durante, 2006;Hatzi et al, 2006;M'Kacher et al, 2023]. Using calyculin A, PCC can be induced with high efficiency in terms of a much higher number of cells to score in comparison to DCA using the same amount of blood [Sun et al, 2020a].…”

Telomere Dysfunction in Pediatric Patients with Differences/Disorders of Sexual Development

“…Peripheral blood lymphocytes were cultured for 72 h, and standard GTG-Banding was performed according to a previous publication [ 41 ]. A total of 50 metaphases from each sample were analyzed at the resolution level of 550 bands.…”