Effect of Low-Dose Ionizing Radiation on the Expression of Mitochondria-Related Genes in Human Mesenchymal Stem Cells.

The concept of hormesis describes a phenomenon of adaptive response to low-dose ionizing radiation (LDIR). Similarly, the concept of mitohormesis states that the adaptive program in mitochondria is activated in response to minor stress effects. The mechanisms of hormesis effects are not clear, but it is assumed that they can be mediated by reactive oxygen species.

Mesenchymal Stem Cells Early Response to Low-Dose Ionizing Radiation.

Introduction: Mesenchymal stem cells (MSCs) are applied as the therapeutic agents, e.g., in the tumor radiation therapy.

1Q12 Loci Movement in the Interphase Nucleus Under the Action of ROS Is an Important Component of the Mechanism That Determines Copy Number Variation of Satellite III (1q12) in Health and Schizophrenia.

Genome repeat cluster sizes can affect the chromatin spatial configuration and function. Low-dose ionizing radiation (IR) induces an adaptive response (AR) in human cells. AR includes the change in chromatin spatial configuration that is necessary to change the expression profile of the genome in response to stress.

Extracellular DNA Containing (dG)n Motifs Penetrates into MCF7 Breast Cancer Cells, Induces the Adaptive Response, and Can Be Expressed.

Background: Oxidized human DNA or plasmid DNAs containing human ribosomal genes can easily penetrate into the breast cancer cells MCF7 and stimulate the adaptive response induction. Plasmid DNA containing a CMV promoter, gene , and the insertion of the human ribosomal genes can be expressed. A hypothesis is proposed: these features of the ribosomal DNA are due to the presence of dGn motifs that are prone to oxidize.

Oxidized Cell-Free DNA Is a Factor of Stress Signaling in Radiation-Induced Bystander Effects in Different Types of Human Cells.

In pathology or under damaging conditions, the properties of cell-free DNA (cfDNA) change. An example of such change is GC enrichment, which drastically alters the biological properties of cfDNA. GC-rich cfDNA is a factor of stress signaling, whereas genomic cfDNA is biologically inactive.

Copy Number Variation of Human Satellite III (1q12) With Aging.

Human satellite DNA is organized in long arrays in peri/centromeric heterochromatin. There is little information about satellite copy number variants (CNVs) in aging and replicative cell senescence (RS). Biotinylated pUC1.

Ribosomal DNA as DAMPs Signal for MCF7 Cancer Cells.

The cell free ribosomal DNA (cf-rDNA) is accrued in the total pool of cell free DNA (cfDNA) in some non-cancer diseases and demonstrates DAMPs characteristics. The major research questions: (1) How does cell free rDNA content change in breast cancer; (2) What type of response in the MCF7 breast cancer cells is caused by cf-rDNA; and (3) What type of DNA sensors (TLR9 or AIM2) is stimulated in MCF7 in response to the action of cf-rDNA? CfDNA and gDNA were isolated from the blood plasma and the cells derived from 38 breast cancer patients and 20 healthy female controls. The rDNA content in DNA was determined using non-radioactive quantitative hybridization.

Increased Transfection of the Easily Oxidizable GC-Rich DNA Fragments into the MCF7 Breast Cancer Cell.

Objective: Easily oxidizable GC-rich DNA (GC-DNA) fragments accumulate in the cell-free DNA (cfDNA) of patients with various diseases. The human oxidized DNA penetrates the MCF7 breast cancer cells and significantly changes their physiology. It can be assumed that readily oxidizable GC-DNA fragments can penetrate the cancer cells and be expressed.

Antioxidant Properties of Fullerene Derivatives Depend on Their Chemical Structure: A Study of Two Fullerene Derivatives on HELFs.

Oxidative stress is a major issue in a wide number of pathologies (neurodegenerative, cardiovascular, immune diseases, and cancer). Because of this, the search for new antioxidants is an important issue. One of the potential antioxidants that has been enthusiastically discussed in the past twenty years is fullerene and its derivatives.

Changes of and /NF-B Expression Levels Induced by Cell-Free DNA in Different Cell Types.

Cell-free DNA (cfDNA) is a circulating DNA of nuclear and mitochondrial origin mainly derived from dying cells. Recent studies have shown that cfDNA is a stress signaling DAMP (damage-associated molecular pattern) molecule. We report here that the expression profiles of cfDNA-induced factors NRF2 and NF-B are distinct depending on the target cell's type and the GC-content and oxidation rate of the cfDNA.

Low-Dose Ionizing Radiation Affects Mesenchymal Stem Cells via Extracellular Oxidized Cell-Free DNA: A Possible Mediator of Bystander Effect and Adaptive Response.

We have hypothesized that the adaptive response to low doses of ionizing radiation (IR) is mediated by oxidized cell-free DNA (cfDNA) fragments. Here, we summarize our experimental evidence for this model. Studies involving measurements of ROS, expression of the NOX (superoxide radical production), induction of apoptosis and DNA double-strand breaks, antiapoptotic gene expression and cell cycle inhibition confirm this hypothesis.

Oxidized extracellular DNA suppresses nitric oxide production by endothelial NO synthase (eNOS) in human endothelial cells (HUVEC).

Circulating DNA from patients with cardiovascular diseases reduce the synthesis of NO in endothelial cells, which is probably related to oxidative modification of DNA. To test this hypothesis, HUVEC cells were cultured in the presence of DNA containing ~1 (nonoxidized DNA), 700, or 2100 8-oxodG/10(6) nucleosides. Nonoxidized DNA stimulated the synthesis of NO, which was associated with an increase in the expression of endothelial NO synthase.

An exposure to the oxidized DNA enhances both instability of genome and survival in cancer cells.

Background: Cell free DNA (cfDNA) circulates throughout the bloodstream of both healthy people and patients with various diseases and acts upon the cells. Response to cfDNA depends on concentrations and levels of the damage within cfDNA. Oxidized extracellular DNA acts as a stress signal and elicits an adaptive response.

Oxidized DNA induces an adaptive response in human fibroblasts.

Cell-free DNA (cfDNA) released from dying cells contains a substantial proportion of oxidized nucleotides, thus, forming cfDNA(OX). The levels of cfDNA(OX) are increased in the serum of patients with chronic diseases. Oxidation of DNA turns it into a stress signal.

Oxidized extracellular DNA as a stress signal in human cells.

The term "cell-free DNA" (cfDNA) was recently coined for DNA fragments from plasma/serum, while DNA present in in vitro cell culture media is known as extracellular DNA (ecDNA). Under oxidative stress conditions, the levels of oxidative modification of cellular DNA and the rate of cell death increase. Dying cells release their damaged DNA, thus, contributing oxidized DNA fragments to the pool of cfDNA/ecDNA.

[DNA-signaling pathway mediating development of a radiation-induced bystander effect in human cells].

Low doses of ionizing radiation induce the adaptive effect (AE) development in human cells which is followed by a number of cell responses. These responses can be transmitted from irradiated cells to non-irradiated ones (bystander effect, BE). The major role in radiation-induced BE is played by an oxidative stress (OS) and a DNA-signaling pathway, in which extracellular DNA fragments (ecDNA) are the factors of stress-signalization.

[Surgical treatment of an acute non-biliary aseptic necrotizing pancreatitis].

The results of treatment of 345 patients, operated on for an acute nonbiliary aseptic necrotic pancreatitis, are adduced. There was established, that rejection to perform an early open access operations with simultaneous application of modern miniinvasive procedures for peritonitis of the enzyme origin (laparoscopy, laparocentesis), an acute aseptic accumulations of liquid in bursa omentalis and cellular tissue of retroperitoneal space, pancreatic pseudocysts (puncture-drainage interventions under ultrasonographic guidance) and as well as direct operative interventions on pancreatic gland and cellular tissue of retroperitoneal space, using extraperitoneal miniaccesses in presence of sequesters, have permitted to lower postoperative lethality from 15.2 to 4.

[Delayed appearance of hypertension in spontaneously hypertensive rat (SHR) injected with CpG-rich DNA early in ontogenesis].

In this study we have investigated properties of blood serum extracellular DNA (cell-free DNA) from patients with essential arterial hypertension (AH). Cell-free DNA concentration was not changed in the control AH group compared to norma (healthy donors) but fragments of CpG-rich cell-free DNA marker content were increased at transcribed area of ribosomal repeat (TArDNA, CpG-DNA). To evaluate effect of CpG-DNA on AH development in 2-day SHR line and in control normotensive line (WKY), 700 ng of human TArDNA single subcutaneous injection were inoculated to obtain anti-CpG-DNA polyclonal antibodies.

An extracellular DNA mediated bystander effect produced from low dose irradiated endothelial cells.

The human umbilical vein endothelial cells culture was exposed to X-ray radiation in a low dose of 10cGy. The fragments of extracellular genomic DNA (ecDNA(R)) were isolated from the culture medium after the short-term incubation. A culture medium of unirradiated endothelial cells was then supplemented with ecDNA(R), followed by analysing the cells along the series of parameters (bystander effect).

Extracellular DNA affects NO content in human endothelial cells.

Fragments of extracellular DNA are permanently released into the blood flow due to cell apoptosis and possible de novo DNA synthesis. To find out whether extracellular DNA can affect the synthesis of nitric oxide (NO), one of key vascular tone regulators, we studied in vitro effects of three artificial DNA probes with different sequences and 10 samples of extracellular DNA (obtained from healthy people and patients with hypertension and atherosclerosis) on NO synthesis in endothelial cell culture (HUVEC). For detection of NO in live cells and culture medium, we used a NO-specific agent CuFL penetrating into the cells and forming a fluorescent product FL-NO upon interaction with NO.

Enhanced expression of iNOS in human endothelial cells during long-term culturing with extracellular DNA fragments.

NO synthesis by endothelial cells plays an important role in normal function of the cardiovascular system. This work was designed to evaluate the role of variations in properties of extracellular DNA in the regulation of NO synthesis. We studied the effect of four DNA samples with various base sequences (50 ng/ml) on functional activity of endothelial cells HUVEC during 24-h culturing.

[Bystander effect development in human mesenchymal stem cells after exposure to adaptive dose of X-radiation].

Transposition and mutual approaching of pericentromeric loci 1q12 of homological chromosomes from the nuclear membrane towards the nuclear centre as well as activation of the chromosomal nucleolus-forming regions (NFR) are observed in human mesenchymal stem cells (hMSCs) as an initial stages of the adaptive response (AR) after exposure to low doses of X-radiation (10 cGy). All these reactions are also induced after addition of cultivation medium from irradiated cells to intact bystander-cells and this phenomenon called bystander effect (BE). Recently the same AR and BE induction results were obtained for human G0-lymphocytes.

[The response of human cancer stem cells on low-dose X-ray exposure].

Recently we found that transposition of homologous chromosomes 1q12 loci towards the nuclear centre and activation of the chromosomal nucleolus-forming regions (NFR) are observed in human lymphocytes after exposure to low doses of X-radiation (10 cGy). These cell reactions were studied for human breast cancer stem cell cultures. There are two cell types in cell culture from single donor: with two (type 1) and three (type 2) loci of 1q12.

Oxidative stress as a significant factor for development of an adaptive response in irradiated and nonirradiated human lymphocytes after inducing the bystander effect by low-dose X-radiation.

X-radiation (10cGy) was shown to induce in human lymphocytes transposition of homologous chromosomes loci from the membrane towards the centre of the nucleus and activation of the chromosomal nucleolus-forming regions (NFRs). These effects are transmitted by means of extracellular DNA (ecDNA) fragments to nonirradiated cells (the so-called bystander effect, BE). We demonstrated that in the development of the BE an important role is played by oxidative stress (which is brought about by low radiation doses and ecDNA fragments of the culture medium of the irradiated cells), by an enzyme of apoptosis called caspase-3, and by DNA-binding receptors of the bystander cells, presumably TLR9.