Abstract
BackgroundEnvironmental risk factors have been shown to alter DNA copy number variations (CNVs). Recently, CNVs have been described to arise after low-dose ionizing radiation in vitro and in vivo. Development of cost- and size-effective laser-driven electron accelerators (LDEAs), capable to deliver high energy beams in pico- or femtosecond durations requires examination of their biological effects. Here we studied in vitro impact of LDEAs radiation on known CNV hotspots in human peripheral blood lymphocytes on single cell level.ResultsHere CNVs in chromosomal regions 1p31.1, 7q11.22, 9q21.3, 10q21.1 and 16q23.1 earlier reported to be sensitive to ionizing radiation were analyzed using molecular cytogenetics. Irradiation of cells with 0.5, 1.5 and 3.0 Gy significantly increased signal intensities in all analyzed chromosomal regions compared to controls. The latter is suggested to be due to radiation-induced duplication or amplification of CNV stretches. As significantly lower gains in mean fluorescence intensities were observed only for chromosomal locus 1p31.1 (after irradiation with 3.0 Gy variant sensitivites of different loci to LDEA is suggested. Negative correlation was found between fluorescence intensities and chromosome size (r = − 0.783, p < 0.001) in cells exposed to 3.0 Gy irradiation and between fluorescence intensities and gene density (r = − 0.475, p < 0.05) in cells exposed to 0.5 Gy irradiation.ConclusionsIn this study we demonstrated that irradiation with laser-driven electron bunches can induce molecular-cytogenetically visible CNVs in human blood leukocytes in vitro. These CNVs occur most likely due to duplications or amplification and tend to inversely correlate with chromosome size and gene density. CNVs can last in cell population as stable chromosomal changes for several days after radiation exposure; therefore this endpoint can be used for characterization of genetic effects of accelerated electrons. These findings should be complemented with other studies and implementation of more sophisticated approaches for CNVs analysis.
Highlights
Environmental risk factors have been shown to alter DNA copy number variations (CNVs)
Negative correlation was found between fluorescence intensity and chromosome size (r = − 0.783, p < 0.001) in cells exposed to 3.0 Gy irradiation and between gene density (r = − 0.475, p < 0.05) in cells exposed to 0.5 Gy irradiation
In summary, we have shown that irradiation with laser-driven electron bunches can induce Copy number variations (CNVs) in human blood leukocytes in vitro
Summary
Environmental risk factors have been shown to alter DNA copy number variations (CNVs). Copy number variations (CNVs) that arise due to deletions and duplications in the genome are major contributors to genetic diversity in human population [1] These changes may lead to phenotypic expression and/ or various diseases (cancer, infertility, neurodevelopmental disorders etc.) [2,3,4], have adaptive effects [5], or can Recent achievements in the field of particle acceleration technologies has led to development of cost- and size-effective laser-driven electron accelerators (LDEAs) [11, 12]. The frequency of de novo CNVs was significantly elevated in offspring of laboratory mice, exposed to ionizing radiation [9], as well as in the progeny of a human subpopulation accidentally exposed during a radiological accident [10]
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