Natalija Gabruseva

Telomere length in Chernobyl accident recovery workers in the late period after the disaster.

The outcome of the Chernobyl nuclear power plant (CNPP) accident was that a huge number of people were exposed to ionizing radiation. Previous studies of CNPP clean-up workers from Latvia revealed a high occurrence of age-associated degenerative diseases and cancer in young adults, as well as a high mortality as a result of cardiovascular disorders at age 45–54 years. DNA tandem repeats that cap chromosome ends, known as telomeres, are sensitive to oxidative damage and exposure to ionizing radiation. Telomeres are important in aging processes and carcinogenesis. The aim of this study was to investigate the long-term effect of protracted ionizing radiation exposure on telomere length in CNPP clean-up workers. Relative telomere length (RTL) was measured in peripheral blood leukocytes of 595 CNPP clean-up workers and 236 gender- and age-matched controls using real-time quantitative polymerase chain reaction (q-PCR). Close attention was paid to participation year and tasks performed during the workers stay in Chernobyl, health status, and RTL differences between subgroups. Telomere shortening was not found in CNPP clean-up workers; on the contrary, their RTL was slightly greater than in controls (P = 0.001). Longer telomeres were found in people who worked during 1986, in those undertaking ‘dirty’ tasks (digging and deactivation), and in people with cancer. Shorter telomeres appeared frequently in those with cataract, osteoporosis, atherosclerosis, or coronary heart disease. We conclude that the longer telomeres revealed in people more heavily exposed to ionizing radiation probably indicate activation of telomerase as a chromosome healing mechanism following damage, and reflect defects in telomerase regulation that could potentiate carcinogenesis.

Fluorescent Characteristics of Blood Leukocytes of Patients with Malignant and Nonmalignant Diseases

Properties of the naphthalic acid derivative 3-isopropyloxy-6-morpholino-2-phenilphenalen-1-ona (PMPH) as a potential fluorescent probe were investigated. Spectral characteristics of the compound in different solvents as well as their binding to model lipid membranes (liposomes) and human peripheral blood mononuclear cells (lymphocytes) were determined. The fluorescence was found to be sensitive to polarity changes in the environment. Distinctions were observed in the spectral characteristics of the investigated compound when bound to liposomes and peripheral blood mononuclear cells of healthy donors, and patients with malignant and nonmalignant diseases. It was established that spectral characteristics of PMPH in cell suspension qualitatively characterize its structural and functional alterations during pathologic phenomena and correlate directly with the clinical view of disease. PMPH is shown to be a prospective method for screening for various pathologies.

Structural Changes in Lymphocytes Membrane of Chernobyl Clean-up Workers from Latvia

ABM (3-aminobenzanthrrone derivative) developed at the Riga Technical University, Riga, Latvia) has been previously shown as a potential probe for determination of the immune state of patients with different pathologies .The fist study (using probe ABM) of peripheral blood mononuclear cells (PBMC) membranes of 97 Chernobyl clean-up workers from Latvia was conducted in 1997. Now we repeatedly examine the same (n = 54) individuals in dynamics. ABM spectral parameters in PBMC suspension, fluorescence anisotropy and blood plasma albumin characteristics were recorded. In 1997 screening showed 5 different patterns of fluorescence spectra, from which in 2007 we obtained only two. These patterns of spectra had never been previously seen in healthy individuals or patients with tuberculosis, multiple sclerosis, rheumatoid arthritis, etc., examined by us. Patterns of ABM fluorescence spectra are associated with membrane anisotropy and conformational changes of blood plasma albumin. We observed that in dynamics 1997–2007 the lipid compartment of the membrane became more fluid while the lipid-protein interface became more rigid. The use of probe ANS and albumin auto-fluorescence allowed show conformational alterations in Chernobyl clean-up workers blood plasma. It is necessary to note that all investigated parameters significantly differ in observed groups of patients. These findings reinforce our understanding that that the cell membrane is a significant biological target of radiation. The role of the membrane in the expression and course of cell damage after radiation exposure must be considered. So ten years dynamic of PBMC membrane characteristics by ABM (spectral shift and anisotropy indexes) in Chernobyl clean-up workers reveal progressive trend toward certain resemblance with those of chronic B-cell lymphoid leukemia.

Fluorescent Study of Human Blood Plasma Albumin Alterations Induced by Ionizing Radiation

The use of hydrophobic fluorescent probe ABM (benzanthrone derivative) and albumin autofluorescence allowed show conformational alterations in Chernobyl clean-up workers blood plasma. Results obtained in 1996–1997 suggest that acidic expansion of plasma albumin takes place. Latest data (2006–2008) result in splitting of albumin alterations onto two stages - acidic expansion and N-F transition. The N-F transition is accompanied by the blue shift of fluorescence spectra and dehydration of tryptophanyl region of albumin molecule. In 2007 obtained.patterns of ABM spectra had never been previously seen in examined healthy individuals or patients with tuberculosis, multiple sclerosis, rheumatoid arthritis, etc. Patterns of ABM fluorescence spectra are associated with conformational changes of blood plasma albumin. The use of probe ABM and albumin auto-fluorescence allowed show conformational alterations in albumin of Chernobyl clean-up workers blood plasma. It is necessary to note that all investigated parameters significantly differ in observed groups of patients. These findings reinforce our understanding that the blood plasma albumin is a significant biological target of radiation. It may be concluded that fluorescence characteristics are representative of radiation induced albumin alterations and its carrier function.

Antioxidant therapy and its stability on Chernobyl clean-up workers

This paper describes the effects of prolonged antioxidant therapy, its stability and association with spectral parameters of the fluorescent probe ABM in blood plasma and indices of albumin auto-fluorescence in Chernobyl clean-up workers from Latvia. Patients were divided into two groups. Group 1 received placebos of identical appearance to antioxidants. Group 2 received antioxidants (vitamin E + selenium + ibuprofen). Individuals were tested three times: before supplementation of antioxidants, after therapy and one year after supplementation interruption. Applied therapy improves oxidant/antioxidant status of individuals. Interruption of therapy after one year leads to significant decrease of cellular immunity. In the group receiving antioxidants it is not so expressed compared with data from the placebos group. Changes in blood plasma and its structural and functional properties detected by ABM strongly correlated with the oxidant/antioxidant (immune) status of individuals. This behaviour of ABM could be useful in reflecting alterations of cellular immunity. Questions related to more detailed and prolonged antioxidant therapy need closer investigation.

Long-term effects of low doses of ionising radiation on Chernobyl clean-up workers from Latvia

Around 6000 inhabitants (20-49 years old in 1986) of Latvia took part in clean-up work in Chernobyl from 1986 till 1991. Most of them were officially documented as recipients of ionising radiation exposure (1-50 cGy). ABM (a 3-aminobenzanthrone derivative developed at the Riga Technical University, Riga, Latvia) has been previously shown to be a potential probe for determining the immune state of patients with different pathologies. The first study (using ABM) of Peripheral Blood Mononuclear Cell (PBMC) membranes of Chernobyl clean-up workers (n-97) from Latvia was conducted in 1996-1997. In 2006-2007 we examined the same (n = 54) individuals. Lipid peroxidation, ABM and ANS spectral parameters in PBMC suspension, fluorescence anisotropy and blood plasma albumin characteristics were recorded. In 1997 screening showed five different patterns of fluorescence spectra, but in 2007 we obtained only four. These patterns of spectra had never been seen previously in healthy individuals or patients with tuberculosis, multiple sclerosis, rheumatoid arthritis, etc., examined by us. The patterns of ABM fluorescence spectra were associated with membrane anisotropy and conformational changes of blood plasma albumin. It is necessary to note that all investigated parameters significantly differed in the observed groups of patients. These findings reinforce our understanding that the cell membrane is a significant biological target of radiation. These studies reveals a progressive trend towards certain resemblances to PBMC membranes of chronic B-cell lymphoid leukaemia and protein coformational alterations.

Fluorescent Probe ABM and Estimation of Immune State in Patients with Different Pathologies (Review Article)

The fluorescent probe ABM (3-aminobenzanthrone derivative) one of the fluorescent probes synthesized in Riga Technical University proved to be an excellent, independent model for studying cell membranes. In our work we have investigated the possibility of using the fluorescent probe ABM for detection of immune state in patients with different pathologies. There is a strong correlation among all studied ABM spectral parameters, immunological characteristics, clinical and laboratory investigations of the all observed patients groups. The obtained results suggest that ABM spectral parameters in cell suspension reflect the alterations of the cellular mechanisms of immunity. Therefore fluorescent method could be used as preliminary screening test in immune diagnostics instead of more expensive, time consuming methods (subset detection, radioisotope method etc.) used as routine in clinics. Spectral parameters of ABM reflect a wide range of interrelated (interdependent) characteristics of cells (physico-chemical state and microviscosity of membrane, proliferating and lipid metabolic activity of cells, distribution of cells among subsets). The observed change of the studied parameters reflects alterations of the cellular mechanisms of immunity which is a main focus for its application as preliminary screening test in immune diagnostics. The fluorescence based method is sensitive, less expensive and time consuming, technically simple and convenient.

Refractive properties of separate erythrocytes of Chernobyl clean-up workers at different pH

This study is focused on the modifications in erythrocytes of Chernobyl nuclear power plant accident clean-up workers as a late health effect of short-term impact of high level radioactive contamination. As a result, a new method based on erythrocyte refractive index properties at different pH has been elaborated.