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.

[The maternal effect in infantile autism: elevated DNA damage degree in patients and their mothers].

Infantile autism is a common disorder of mental development, which is characterized by impairments in the communicative, cognitive and speech spheres and obsessional stereotyped behaviour. Although in most cases, pathogenic factors remain unclear, infantile autism has a significant hereditary component, however, its etiology is also under the influence of environmental factors, including the condition of the mother's body during pregnancy ("maternal effect"). Oxidative stress is assumed to play a key role in the pathogenesis of infantile autism.

GC-Rich Extracellular DNA Induces Oxidative Stress, Double-Strand DNA Breaks, and DNA Damage Response in Human Adipose-Derived Mesenchymal Stem Cells.

Background: Cell free DNA (cfDNA) circulates throughout the bloodstream of both healthy people and patients with various diseases. CfDNA is substantially enriched in its GC-content as compared with human genomic DNA.

Principal Findings: Exposure of haMSCs to GC-DNA induces short-term oxidative stress (determined with H2DCFH-DA) and results in both single- and double-strand DNA breaks (comet assay and γH2AX, foci).

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.

Post-transcriptional gene silencing and virus resistance in Nicotiana benthamiana expressing a Grapevine virus A minireplicon.

Grapevine virus A (GVA) is closely associated with the economically important rugose-wood disease of grapevine. In an attempt to develop GVA resistance, we made a GFP-tagged GVA-minireplicon and utilized it as a tool to consistently activate RNA silencing. Launching the GVA-minireplicon by agroinfiltration delivery resulted in a strong RNA silencing response.

[Clinical-immunological and ecological research in diabetic retinopathy].

Two hundred and ninety-six patients with diabetic retinopathy (DR) were examined: conservative therapy and laser coagulation of the retina were applied in 120 and 176 of them, respectively. The ecological situation in the residence region and its impact on the morbidity and immune status of DR patients were analyzed. The comfort degree of the environment and the level of anthropogenic contamination affect the morbidity and immunogram results.

[Clinical-immunological and epidemiological studies in high complicated myopia].

A total of 100 patients with high complicated myopia were examined. Immunodeficiency syndrome and signs of autosensitization were revealed in this patient population. Analysis of morbidity and its relationship with some environmental factors and characteristics of the activity of public health system showed that the morbidity was related to increased radioactivity and to unsatisfactory status of water in a region, and that increase of the number of medical workers may help reduce the morbidity.

[Cytogenetic damage and the degree of reparative synthesis in the lymphocytes of chemical industry workers].

A thiophosphamide-induced increase of repair DNA-synthesis in lymphocytes in shown. To include cytogenetic studies in a genetic- and epidemiologic programme of genetic monitoring to make a complex assessment of health status of chemical industry workers is recommended.

[A theory on the role of immunologic factors in the pathogenesis of primary glaucoma].

Basing on the literature data and their own clinical, immunomorphologic, and immunochemical findings in glaucoma patients and normal subjects, the authors suggest a concept on the immune factor contribution to the pathogenesis of primary open-angle glaucoma. According to the scheme they suggest, of primary importance in the development of autoimmune reactions in glaucoma are the following factors: changed antigenic specificity of the drainage zone tissues, resultant from involution processes; impaired immune homeostasis, effects of various internal and environmental factors. The pathogenetic role of autoimmune reactions and immunity system regulatory mechanism disorders is explained.

[Experience with the surgical treatment of the sequelae of uveal tract diseases].

The paper describes results of investigation of immunologic reactivity and analysis of outcomes after surgical treatment of patients with chronic anterior uveitis (14 persons), the Fuchs' syndrome (16 persons), pseudoexfoliative syndrome (25 persons) as compared with a control group (50 persons). Immunocorrection of patients with the Fuchs' syndrome was attempted, and analysis of the immunologic status before and after treatment by means of sodium nucleinate immunomodulator and traditional therapy was made. Cataract extraction was performed separately or in combination with sinusotrabeculectomy in case of uveal glaucoma.

[The induction and elimination of cytogenetic disorders in monkey lymphocytes following thiophosphamide action].

The dynamics of sister chromatid exchanges and chromosome aberrations in lymphocyte of monkey has been investigated after a thiophosphamide exposure. The process of induction and elimination of cytogenetic damages was described by the mathematical model. Developing the model in detail will allow to make a cytogenetic prognosis of remote consequences of mutagenic exposure.

[Dynamics of sister chromatid exchange after in vivo exposure to thiophosphamide].

Thiophosphamide (T) was i.v. administered into New Zealand rabbit (4 mg/kg).

[Dynamics of the frequencies of sister chromatid exchange and chromosome aberrations in vivo].

2.4 and 6 mg/kg thiophosphamide (T) was administered intravenously to New Zealand rabbits. A decrease in sister chromatid exchange (SCE) and chromosome aberration (CA) rate began immediately after the mutagenic action of T was over.

[Quantitative comparison of the cytogenetic effect of thiophosphamide during in vivo and in vitro action on monkey lymphocytes].

Mutagenic in vivo and in vitro effects were compared quantitatively by the investigation of sister chromatid exchange (SCE) rate and chromosomal aberrations caused by thiophosphamide in macaca rhesus lymphocytes. The integral of thiophosphamide concentration in the blood or culture fluid by a certain time period was used for the estimation of the dose of mutagenic exposure. It was shown that the dose-response relationships and corresponding regression coefficients were similar when the in vivo and in vitro results were compared.

[Comparison of the cytogenetic effects of cyclophosphamide on monkey lymphocytes in vivo and in vitro].

The comparative in vivo and in vitro study of chromosomal aberrations and SCE induced by cyclophosphamide (CP) in macaca rhesus lymphocytes was performed. The dose of mutagenic exposure for quantitative estimation of effects was determined as a product of concentration of alkylating CP metabolites on the exposure time. The mutagenic effect caused by the same doses of CP (CP metabolites) appeared similar in vivo and in vitro.

[Ratio of the frequency of chromosome aberrations and sister chromatid exchanges to the dose of the mutagenic exposure to cyclophosphamide in vivo and in vitro].

Cyclophosphamide (CP) and its metabolites were used to compare the rate of chromosomal aberrations (CA) and sister chromatid exchange (SCE) in the rabbit lymphocytes in vivo and in vitro. The dose-dependent increase of cytogenetic effects rate appeared to be of linear and exponential dependence for SCE and CA, respectively, both in vivo and in vitro. The regression equation coefficients coincided in in vivo and in vitro experiments.

Cytogenetic effects of cyclophosphamide on human lymphocytes in vivo and in vitro.

A comparative study of cytogenetic effects in human lymphocytes caused in vivo by cyclophosphamide (CP) after intravenous injection and in vitro by exposure of plasma of the same patients was carried out. It was found that the frequency of induced chromosome aberrations (CA) and sister-chromatid exchanges (SCE) increased linearly for SCE and exponentially for CA within the 'dose' of alkylating activity of CP metabolites. Parameters of 'cytogenetic effect-dose' in vivo and in vitro coincided.

[Induction of chromosome aberrations in human lymphocytes by cyclophosphamide action in vivo and in vitro].

The dose dependences of chromosome aberrations rate were investigated in lymphocytes of oncological patients after cyclophosphamide (CP) administration. It was shown that the rate of chromosome aberrations and the number of disruptions per cell in vivo and in vitro increases exponentially with the dose. At the same time, the parameters of regression equations coincide.

Alterations in the baseline sister-chromatid exchange frequency in human lymphocyte culture following a number of cell divisions.

A significant decrease in the baseline of sister-chromatid exchanges (SCEs) was observed in cultured human lymphocytes, if 5-bromodeoxyuridine (BrdU) was added after 60 h of culture, and the cells were harvested at least 24-30 h after BrdU exposure. This decrease is supposed to occur if at least one cell division takes place before the addition of BrdU. For cytogenetic monitoring of mutagenic environmental factors, using human lymphocyte cultures, it is assumed that two time periods are sufficient for comparison.