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DNA repair in modeled microgravity: Double strand break rejoining activity in human lymphocytes irradiated with γ-rays

MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS (2009)

期刊

MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS

卷 663, 期 1-2, 页码 32-39

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DOI: 10.1016/j.mrfmmm.2009.01.002

关键词

Ionising radiation; Modeled microgravity; Double strand breaks; gamma-H2AX foci; Human PBL

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Biotechnology & Applied Microbiology Genetics & Heredity Toxicology

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Italian Space Agency

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摘要

Cell response to ionising radiation depends, besides on genetic and physiological features of the biological systems, on environmental conditions occurring during DNA repair. Many data showed that microgravity, experienced by astronauts during space flights or modeled on Earth, causes apoptosis, cytoskeletal alteration, cell growth inhibition, increased frequency of mutations and chromosome aberrations. In this study, we analysed the progression of the rejoining of double strand breaks (DSBs) in human peripheral blood lymphocytes (PBLs) irradiated with gamma-rays and incubated in static condition (1g) or in modeled microgravity, (MMG). gamma-H2AX foci formation and disappearance, monitored during the repair incubation, showed that the kinetics of DSBs rejoining was different in the two gravity conditions. The fraction of foci-positive cells decreased slower in MMG than in 1g at 6 and 24h after irradiation (P<0.01) and the mean number of gamma-H2AX foci per nucleus was significantly higher in MMG than in 1g at the same time-points (P<0.001). In the same samples we determined apoptotic level and the rate of DSB rejoining during post-irradiation incubation. A significant induction of apoptosis was observed in MMG at 24 h after irradiation (P < 0.001), whereas at shorter times the level of apoptosis was slightly higher in MMG respect to 1g. In accordance with the kinetics of gamma-H2AX foci, the slower rejoining of radiation-induced DSBs in MMG was observed by DNA fragmentation analyses during the repair incubation; the data of pulsed-field gel electrophoresis assay showed that the fraction of DNA released in the gel was significantly higher in PBL incubated in MMG after irradiation with respect to cells maintained in I g. Our results provide evidences that MMG incubation during DNA repair delayed the rate of radiation-induced DSB rejoining, and increased, as a consequence, the genotoxic effects of ionising radiation. (C) 2009 Elsevier B.V. All rights reserved.

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Increased Gene Targeting in Hyper-Recombinogenic LymphoBlastoid Cell Lines Leaves Unchanged DSB Processing by Homologous Recombination

Emil Mladenov, Katja Paul-Konietzko, Veronika Mladenova, Martin Stuschke, George Iliakis

Summary: Sophisticated mechanisms have evolved in higher eukaryotes to repair DNA double-strand breaks (DSBs) through different repair pathways. These repair pathways not only contribute to DSB repair, but also influence the integration of foreign DNA or rearrangement of genetic information in cells. However, the efficiency of gene targeting is generally low in somatic cells due to random integration of DNA fragments. In contrast, embryonic stem cells and certain lymphoblastic cell lines show increased gene-targeting efficiency.

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