Ionizing Radiation-Induced Genomic Instability in CHO cells Is Followed by Selection of Radioresistant Cell Clones

Abstract

The DNA comet assay (neutral version) showed that irradiation of CHO cells in a dose of 1 Gy (gamma-radiation, (60)Co) is followed by an increase in the degree of DNA fragmentation. These changes were observed immediately after irradiation and on days 7-21. On days 2-4 and 23-28 after irradiation, the degree of DNA fragmentation in the descendants of irradiated cell did not differ from that in control samples. The increase in the degree of DNA fragmentation on days 7-21 probably results from induction of apoptosis. This assumption is confirmed by the study of cell death. The sensitivity of cells to repeated irradiation in a dose of 10 Gy significantly increased on days 9, 11, 16, and 18 after irradiation. However, these cells were resistant to repeated irradiation on days 21-28. Our results confirm the hypothesis that genomic instability is a selective mechanism, which mediates the formation of radioresistant cell clones.

Residual γH2AX foci induced by low dose x-ray radiation in bone marrow mesenchymal stem cells do not cause accelerated senescence in the progeny of irradiated cells

“…Indeed, we did not observe increased rates of γН2АХ foci at passages 3 and 5 after irradiation, implying that irradiated MSCs (at least at the doses used here) do not transmit the residual γH2AX foci through the cell divisions, as described by Vaurijoux et al [ 71 ]. At the same time the observed high rates of γН2АХ foci in the progeny (passages 8 and 11) of 1000 mGy-exposed cells is consistent with radiation-induced genome instability [ 72 , 73 ] or accelerated cellular senescence [ 74 , 75 ]. Genome instability and senescence are not necessarily linked.…”

Inside the hypoxic tumour: reprogramming of the DDR and radioresistance

“…GI is associated with both tumour aggressivity and progression 132 , as well as RR 133 , 134 , though only a few studies have linked it to hypoxia-induced RR. The connection between GI and RR is mostly indirect, with GI thought to lead to the development of radioresistant clones following periods of chromosomal rearrangements 135 , 136 . A number of studies have shown development of GI in hypoxia 66 , a feature particularly relevant for tumours lacking functional p53 as is common in many hypoxic cancers, as apoptosis will be less likely to occur 137 .…”

The Role of Mitochondria in the Development of Radiation-Induced Oxidative Stress in K562 Leukemia Cells

“…Active oxygen species are the main cause of the destructive effect of radiation [14]. Radiation exposure can cause delayed effects because of the genome instability emergence [1]. Genetically unstable cell strains can cause malignant transformation of normal cells and emergence of radiation-resistant cancer cell clones [1].…”

“…Radiation exposure can cause delayed effects because of the genome instability emergence [1]. Genetically unstable cell strains can cause malignant transformation of normal cells and emergence of radiation-resistant cancer cell clones [1]. Genetically unstable cells are characterized by hyperproduction of ROS, presumably generated by the mitochondria [2].…”

“…The most sensitive to ionizing radiation is DNA, which manifests in the formation of strand ruptures resulting from hydrolytic rupture of phosphodiester bond after free radical transfer from the base to ribose residue [12]. Free-radical damage to DNA cause mutations and genetic instability, this leading, in turn, to formation of radioresistant cell clones [1]. The mitochondrial DNA is less protected from stress exposure than the nuclear DNA [2].…”