The Frequency of Lymphocytes Containing Dumbbell-Shaped Nuclei Depends on Ionizing Radiation Dose and Correlates with Appearance of Chromosomal Aberrations

Abstract

Nuclear anomalies of different types appear in cells in response to the action of ionizing radiation after the passage of the first mitotic division. In this article, we present the results of the study of the frequency of occurrence of three types of nuclear anomalies (“tailed” nuclei, nucleoplasmic bridges, and dumbbell-shaped nuclei) in vitro in human lymphocytes cultured with cytochalasin B when exposed to X-rays at doses of 0.0, 0.1, 0.2, 0.4, 0.5, 0.7, 1.0, 1.5, and 2.0 Gy. To stop the cell cycle of cultured lymphocytes after the first mitotic division, a cytokinesis block was performed using cytochalasin B. Dose-dependent curves of the occurrence of lymphocytes containing “tailed” nuclei, nucleoplasmic bridges, or dumbbell-shaped nuclei after irradiation have been constructed. At the same time, frequencies of occurrence of chromosomal aberrations (dicentric and ring chromosomes) in the culture of lymphocytes exposed to the same radiation doses were studied. Comparison of the frequencies of occurrence of dicentric and ring chromosomes with frequencies of occurrence of nuclear anomalies allows us to conclude that these nuclear anomalies are formed as a result of chromosomal aberrations arising in lymphocytes under the action of ionizing radiation. More than that, most of the chromosomal aberrations are converted into dumbbell-shaped nuclei in vitro in the culture of lymphocytes in the cytochalasin block.

Low-Energy Laser-Driven Ultrashort Pulsed Electron Beam Irradiation-Induced Immune Response in Rats

“…The formation of bilobed lymphocytes after electron beam exposure is an interesting phenomenon, which was first described by cyclotron personnel at the University of Rochester in 1948-1951 [39], and then in humans, who received different doses of radiation [34][35][36][37][38][39][40][41][42][43].…”

Could scoring tailed and dumbbell-shaped nuclei increase the sensitivity of micronucleus analysis as a biomarker of radiation exposure?

“…Berkala Then, if the NPB undergoes a rupture during cytokinesis, it could result in the formation of tailed nuclei (Fig. 1) (Kravtsov et al 2018). In 2014, Kravtsov et al investigated the origin of tailed nuclei using telomere and centromere fluorescence in situ hybridization (FISH).…”

“…In other words, tailed nuclei observed during interphase are produced by the breakdown of chromosomal bridges between dicentric chromosomes. Since the tip of the tail of tailed nuclei contains double-strand breaks (DSB), as identified by the DNA repair system, it can cross-link, form dicentric chromosomes, and generate new NPBs after anaphase (Kravtsov et al 2014, Kravtsov et al 2018.…”

“…Although the origin of dumbbell-shaped nuclei has been associated with the morphological characteristics of amitosis (direct cell division), in which the nuclear components are unequally distributed between the nuclei of daughter cells, the exact mechanism of the formation of this nuclear abnormality remains elusive. Still, Kravtsov and colleagues found that the structure of dumbbell-shaped nuclei is arranged by several NPBs that connects one nucleus to the other (Kravtsov et al 2018). Moreover, they found that the number of cells containing dumbbell-shaped nuclei is a reliable predictor of ionizing radiation dose and correlates with the occurrence of chromosome abnormalities (Kravtsov et al 2018).…”

“…Still, Kravtsov and colleagues found that the structure of dumbbell-shaped nuclei is arranged by several NPBs that connects one nucleus to the other (Kravtsov et al 2018). Moreover, they found that the number of cells containing dumbbell-shaped nuclei is a reliable predictor of ionizing radiation dose and correlates with the occurrence of chromosome abnormalities (Kravtsov et al 2018). Thus, the frequency of lymphocytes bearing dumbbell-shaped nuclei is an attractive measure for biodosimetry testing, especially when one considers that counting of cells with dumbbell-shaped nuclei is much simpler than analysing metaphase chromosomes in cytogenetic assessments (Kravtsov et al 2018).…”