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Open AccessArticle

Doxorubicin-Induced Translocation of mtDNA into the Nuclear Genome of Human Lymphocytes Detected Using a Molecular-Cytogenetic Approach

1
Department of Genetics and Cytology, Yerevan State University, Alex Manoogian 1, Yerevan 0025, Armenia
2
Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Am Klinikum 1, D-07747 Jena, Germany
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(20), 7690; https://doi.org/10.3390/ijms21207690
Received: 28 August 2020 / Revised: 27 September 2020 / Accepted: 14 October 2020 / Published: 17 October 2020
(This article belongs to the Special Issue Structural Variability and Flexibility of the Genome)
Translocation of mtDNA in the nuclear genome is an ongoing process that contributes to the development of pathological conditions in humans. However, the causal factors of this biological phenomenon in human cells are poorly studied. Here we analyzed mtDNA insertions in the nuclear genome of human lymphocytes after in vitro treatment with doxorubicin (DOX) using a fluorescence in situ hybridization (FISH) technique. The number of mtDNA insertions positively correlated with the number of DOX-induced micronuclei, suggesting that DOX-induced chromosome breaks contribute to insertion events. Analysis of the odds ratios (OR) revealed that DOX at concentrations of 0.025 and 0.035 µg/mL significantly increases the rate of mtDNA insertions (OR: 3.53 (95% CI: 1.42–8.76, p < 0.05) and 3.02 (95% CI: 1.19–7.62, p < 0.05), respectively). Analysis of the distribution of mtDNA insertions in the genome revealed that DOX-induced mtDNA insertions are more frequent in larger chromosomes, which are more prone to the damaging action of DOX. Overall, our data suggest that DOX-induced chromosome damage can be a causal factor for insertions of mtDNA in the nuclear genome of human lymphocytes. It can be assumed that the impact of a large number of external and internal mutagenic factors contributes significantly to the origin and amount of mtDNA in nuclear genomes. View Full-Text
Keywords: CBMN assay; doxorubicin; FISH; mtDNA insertion in nuclei; micronuclei CBMN assay; doxorubicin; FISH; mtDNA insertion in nuclei; micronuclei
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Harutyunyan, T.; Al-Rikabi, A.; Sargsyan, A.; Hovhannisyan, G.; Aroutiounian, R.; Liehr, T. Doxorubicin-Induced Translocation of mtDNA into the Nuclear Genome of Human Lymphocytes Detected Using a Molecular-Cytogenetic Approach. Int. J. Mol. Sci. 2020, 21, 7690.

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