The carcinogenic effects of estragole in mice of the earlier unexplored strain ICR has been studied. It has been shown that there is a distinct correlation between the extent of inhibition of glucocorticoid-mediated induction of tyrosine aminotransferase and trypthophan oxygenase after acute administration of estragole and the frequency of liver tumors after estragole exposure. Estragole inhibits the induction of these enzymes only in female mice, but not in male mice and rats. DNA-binding activities of liver-enriched transcription factors were investigated on carcinogen-susceptible and -resistant animals. Estragole decreases the HNF4 (hepatic nuclear factor 4) and FOXA DNA-binding activities only in susceptible female mice, but not in nonsusceptible male mice and rats and does not influence the C/EBP and HNF1 activities. Pentachlorophenol, which prevents the hepatocarcinogenic effect of estragole, abolishes its inhibitory effect on tyrosine aminotransferase and trypthophan oxygenase glucocorticoid induction and restores the FOXA and HNF4 DNA-binding activities. The parallelism between the hepatocarcinogenic effects of estragole and the inhibition of FOXA and HNF4 DNA-binding activities serves as an additional argument for the involvement of these factors in the mechanisms of tumor suppression in the liver.

Content of blood protein carbonyl derivates in rats are determined to assess oxidative modification of protein after destruction of capsaicin-sensitive nerve and change of nitric oxide (NO) level. Deafferentation of these nerves produces increase of the protein carbonyl derivates content. The increase of NO by L-arginine does not affect protein oxidative destruction produced by ablation of capsaicin-sensitive nerve. Selective inhibitor of neuronal synthase NO (n-NOS) 7-nitroindazole (7-NI) results in similar effect. L-NAME increased oxidative destruction of proteins. These results demonstrate that deafferentation of capsaicin-sensitive nerve induces oxidative destruction of proteins. NO has party to mediating oxidative modification of proteins.

In this work, we present the evidences of the involvement of Rdh54 in coordination of DNA repair by several pathways. Previously, we isolated rdh54-29 point mutation demonstrating unique properties different from the full deletion of RDH54 gene. Epistatic interaction between rdh54-29 and apn1delta mutations discloses the function of Rdh54p in the process of base excision repair. However, rdh54-29 mutant exhibits sensitivity to many DNA damaging agents including UV light, methylmethanesulphonate and nitrous acid. Such pleiotrophic effect of rdh54-29 mutation may indicate the role of Rdh54p in the regulation of different DNA repair systems. To check this hypothesis, we estimated the effect of rdh54-29 mutation on recombination and mutagenesis. The data confirm the involvement of Rdh54p in coordination of different DNA repair systems including mutagenic and recombinagenic pathways as well as nucleotide excision repair. Rdh54p presumably operates via chromatin remodulation at the site of damage rendering DNA accessible to the DNA repair enzymes.

Lectins were extracted from the surface of nitrogen-fixing soil bacteria Azospirillum brasilense Sp7 and from its mutant A. brasilense Sp7.2.3 defective in lectin activity. The ability oflectins to stimulate the rapid formation of hydrogen peroxide related to increase of oxalate oxidase and peroxidase activity in the roots of wheat seedlings has been demonstrated. The most rapid induced pathway of hydrogen peroxide formation in the roots of wheat seedlings was the oxalic acid oxidation by oxalate oxidase which is the effect oflectin in under 10 min in a concentration of 10 microg/ml. The obtained results show that lectins from Azospirillum are capable of inducing the adaptation processes in the roots of wheat seedlings.

To study the influence of the COX inhibitor--lornoxicam (LX)--on Toll-like receptor (TLR)-mediated production of proinflammatory and anti-inflammatory cytokines by peripheral blood mononuclear cells (PBMC) from healthy subjects and patients with acute pancreatitis (AP) in vitro.

Daily oral administration to rats of probiotic strain Lactobacillus casei 114001 (L.c.) at dose 2,8 x 10(10) cfu/rat during 8 days reduced oxidative stress and liver lesions, induced by a single intraperitoneal administration of carbon tetrachloride (CCl4) at dose 0.5 ml/kg b.w. It was evidenced by several histopathological and biochemical markers, characteristic for CCl4 toroxicity. Membrane damage by toxin was reduced in rats, treated with L.c.: alanine aminotransferase activity in plasma and nonsedimentable activity of lysosomal enzymes in liver were significantly decreased. Treatment with L.c. resulted in partial recovery of activities of antioxidant enzymes and enzymes of xenobiotic metabolism and full recovery of antioxidant capacity of liver cytosol. High level of activity and expression of proteins heme oxygenase and Nrf2 were maintained.

An antioxidant activity of the water-alcohol extracts of leaves of ten herbs from Western Siberia was studied. In vivo the capability of extracts to protect cells of Escherichia coli against the bacteriostatic action of H2O2 and the influence of the extracts on the expression of the antioxidant gene katG coding catalase-hydroperoxidase I were investigated. In vitro the radical-binding activity with DPhPG (1,1-diphenyl-2-picrylhydrazyl radical), the chelating capability with ferrozine, and total composition of flavonoids and tannins were determined. The extracts of Filipendula stepposa and Limonium gmelinii were characterized by the highest antioxidant activity. According to data, the test extracts could have an antioxidant effect on bacteria in different ways at once including the direct inhibition of ROS (reactive oxygen species), iron ion chelation and antioxidant gene induction.

Nuclear receptors are transcription factors that are essential in embryonic development, cellular differentiation, metabolism. Ligand-regulated nuclear PXR receptor responds to diverse arrays of chemically distinct ligands, xenobiotics, drugs and regulates expression of the genes involved in xenobiotic and drug metabolism. The structural basis of the receptor provides interaction with a variety of ligands which are agonists or antagonists. Nuclear receptors researches are important for design of metabolism regulating drugs and in drug interaction studies.

Interferon gamma (IFNgamma) is known to inhibit proliferation of certain transformed cell lines. Recently, we have demonstrated the transactivation of the epidermal growth factor receptor (EGFR) in response to IFNgamma (Burova et al., 2007) and provided direct evidence for the dependence of IFNgamma-induced EGFR transactivation upon EGFR expression level in epithelial cells (Gonchar et al., 2008). This study examines an antiproliferative effect of IFNgamma on human epithelial cells lines A431 and HeLa which express high levels of EGFR, as well as HEK293, which expresses low levels of EGFR. We characterized the IFNgamma-induced changes in these cells by studying cell growth, the cell cycle and induction of apoptosis. The response to IFNgamma differed in the tested cell lines: cell growth was inhibited in both A431 and HeLa cells, but not in HEK293 cells, as shown by cell counts and MTT. The cell cycle phases analyzed by flow cytometry were disturbed in A431 and HeLa cells in response to IFNgamma. In contrast, IFNgamma treatment did not alter distribution by cell cycle phases in HEK293. Our results indicate that IFNgamma exhibit an antiproliferative effect depending on the increased expression of EGFR in A431 and HeLa cells. Further, it was demonstrated that IFNgamma induced the caspase 3 activation in A431 cells, suggesting an involvement of active caspase 3 in IFNgamma-induced apoptosis.

The effects of growth regulator of the new generation-melamine salt of bis(oxymethyl)phosphine acid (melafen)--on culture growth, pigment and protein content, and the induction of protective chloroplastic chaperone HSP70B in Chlamydomonas reinhardtii CW15 cells were studied. Melafen exhibited 10-30% growth inhibition at 10(-9)-10(-2)% concentration. At 10(-9)-10(-4)% of melafen electrophoretic concentration, the pattern of cellular proteins was similar to the control. The alterations in protein content of algae cells were detected only at 10(-2)% concentration. The content of chlorophyll and carotenoids in melafen-treated cells was 17-40% lower than in the control. Melafen at 10(-9)-109-2)% concentration inhibited HSP70B induction by 39-43% compared to untreated cells. The potential mechanism of melafen effect might involve its influence on nuclear gene expression.

Induction of cellular senescence by various antitumour agents is a promising strategy of cancer treatment. We assessed the ability of sodium butyrate (NaB), a histone deacetylase inhibitor (HDACi), to reactivate the cellular senescence program in either E1A + cHa-Ras-transformed rat embryo fibroblasts with wild-type p53 (ERas(WT)) and in the isogenic cell line where p53 was inactivated due to expression of the potent genetic suppressor element GSE56 (ERas(GSE56)). NaB treatment increased p53 transcriptional activity and induced an irreversible G1/S cell cycle arrest in ERas(WT), but not in ERas(GSE56) cells. By the transient transfections method using reporter luciferase (p53-LUC) constructions, it was shown that p53-LUC activity as a marker of p53 transactivation function did not increase after X-rays exposure of transformants ERas(GSE56). p53 activity in transformants ERas(WT) increased both after irradiation or upon NaB treatment. Interestingly, the expression of senescence-associated beta-galactosidase (SA-beta-Gal), widely used as a marker of senescence, as well as loss of clonogenic ability, were observed in both cell lines following NaB treatment. Thus, our results suggest that induction of p53 transcription activity could be the key determinant of HDACi-induced cell cycle arrest and senescence in transformed cells and provide an additional evidence of SA-beta-Gal invalidity as a sufficient senescence marker.

A putative way of the protective action of cytokinins on the photosynthetic processes in crops experiencing various stress factors is considered. Various cytokinins are characterized. Pathways of the multiple effects of cytokinin preparations mediating the protection of the photosynthetic machinery from stress are described. Cytokinins interact with receptor proteins, and then the signal is transduced to primary cellular targets (primary response genes). These genes, which possess receptor domains, induce synthesis of the corresponding mRNAs and photosynthesis-related proteins of chlorophyll-protein complexes, the electron-transport chain, and carbon metabolism, primarily, the key enzyme ribulose bisphosphate carboxylase/oxygenase. The protective action of cytokinins under stress conditions preserves the structure and function of the photosynthetic apparatus. The application of cytokinins to improving crop yields is discussed.

One of the systems that regulate tissue homeostatis is gap junction intercellular communications (GJIC). Inhibition of GJIC is widely used in experiments as a characteristic of tumor promotion. It is accepted that the down-regulation of GJIC is tightly related with the tumor-promoting properties of carcinogens. In this study, the effect of some carcinogenic polycyclic aromatic hydrocarbons on GJIC in cell cultures of hepatoma 27 lacking cytochrome P450 and Ah receptor was investigated. It was shown that inter 6 compounds studied only benzo/a/pyren and 3-methylcholanthrene were able to inhibit GJIC. We have concluded that an unknown factor is present in hepatoma cells and its interaction with some polycyclic aromatic hydrocarbons results in GJIC inhibition. The investigation of mutual effect of benzo/a/pyrene and non carcinogenic benzo/e/pyrene with similar structure has shown that GJIC inhibition by benzo/a/pyrene is at least double stepped.

Modern immunotherapy has developed powerful tools for mounting antitumor response which nevertheless have had only limited success in clinic. Tumor cells use different mechanisms to escape from immune system. Thus, one of the reasons of unsuccessful immunotherapy might be induction of tolerance of tumor-specific cytotoxic lymphocytes by tumor cells. Previously we have demonstrated expression of HLA-E molecule by the cells of melanoma cell lines. In this paper we have studied HLA-E-dependent mechanism of melanoma cell escape from immune response.

The effect of the nonionic detergent polyethylene glycol octylphenyl ester (Triton X-100, TX-100) on the spring common wheat cultivar Alem was studied under laboratory and field conditions. Treatment of seeds and vegetating plants with 0.1 or 0.01% TX-100 (aqueous solution) changed the spike morphology in all plants of the first posttreatment generation. The changes were inherited by the second generation without additional treatment with TX-100. Square-headed dense spikes with doubled spikelets of the duospiculum type (an additional spikelet at the top of the main one), elongate dense and lax spikes, mid-dense spikes, and fusiform spikes were observed. An epigenetic nature was assumed for the observed changes.

The influence of leucocytic alpha-interferon in concentrations of 0.01, 0.1, 1, 10, and 100 IU/ml on the expression of CD3 complexes by native and photomodified T lymphocytes of human blood has been studied. It was found that the irradiation of suspensions of T cells by UV-light in doses of 151-906 J/m2 increases, and in a dose of 1359 J/m2, reduces the quantity of CD3 complexes on the surface of their membranes. It was shown that the injection of cytokine in concentrations of 0.01-100 IU/ml into a suspension of irradiated T lymphocytes levels off the immunosuppressive action of maximal doses of UV-radiation (1359 J/m2), inducing the recovery and increase in their antigen-recognizing capacity. The data on the antigen-recognizing capacity of UV-irradiated T lymphocytes of human blood, modified by alpha-interferon, enable one to predict the results of seances of autotransfusion of UV-irradiated blood in the case of combined use of UV-irradiation of blood and cytokinotherapy.

Escherichia coli exposure to sublethal antibiotic concentrations induced an increase in cell polyamine contents. Maximum accumulation of putrescine and spermidine in response to antibiotics-induced oxidative stress preceded the increment of cadaverine, the content of which was dependent on the rpoS expression level and reached the maximum in response to fluoroquinolones. The polyamine positive modulating effects on rpoS expression increased in the following order: cadaverine-putrescine-spermidine. The reason for cadaverine accumulation was the increase in activities of lysine decarboxylases CadA and Ldc. High cadaverine accumulation in the cells exposed to fluoroquinolones and cephalosporins resulted in the reduction of porin permeability; so it was considered as a response aimed at cell protection against antibiotic penetration into the cell. Netilmycin, unlike other antibiotics, did not substantially affect the lysine decarboxylase activity and cellular polyamine pools.

The corticotropin-releasing hormone (CRH) family of neuropeptides includes CRH (a 41 amino acid hypothalamic peptide) and urocortin. Corticotropin-releasing factor (CRF), a peptide first isolated from mammalian, plays an important role in the regulation of the pituitary-adrenal axis, and in endocrine, autonomic, immune and behavioral responses to stress. In this study we cloned rat urocortin II (UCNII) cDNA from rat mid-brain by RT-PCR. The rat UCNII clone contained an open reading frame (ORF) coding 109 amino acids which shared 90% and 63% homology with mouse and human homologues, respectively, The expression of UCN HII mRNA is mainly distributed in bone marrow, ovary, uterus, hypophysis, adrenal gland, and skin. In this study, rat recombinant UCN was expressed in E. coli and purified in active form. Furthermore, purified recombinant UCN II protein specifically binds to CRF receptor 2 in rat ROS 17/2.8 and GH3 cells by flow-cytometry analysis. UCN II cDNA clone obtained in this study will be useful for further investigation on behavioral responses to stress in rats.

The effect of melafen, a plant growth regulator of a new generation, on the growth, pigment composition, and expression of nuclear genes Elip1 and Elip2 encoding chloroplast light-stress proteins in barley (Hordeum vulgare L) seedlings was studied. It is shown that the height of seedlings treated with melafen at concentrations of 0.5 x 10(-10) and 0.5 x 10(-8) M increased by approximately 10 and 20%, respectively, as compared to the control. At high concentrations (10(-5) and 10(-3) M), melafen had no effect on the growth of seedlings. The content of chlorophylls and carotenoids in chloroplasts barely differed from the control at all melafen concentrations tested. Reverse transcription-polymerase chain reaction (RT-PCR) showed that melafen did not influence the expression of the nuclear gene encoding the low-molecular-weight plastid stress protein ELIP1. At the same time, the expression of the nuclear gene encoding the high-molecular-weight light-inducible stress protein ELIP2 in the plants treated with melafen at a concentration of 0.5 x 10(-8) M, increased by approximately 70 %. At higher concentrations, melafen suppressed the Elip2 gene expression. Thus, melafen affects the expression of the Elip2 gene, which is involved in the regulation of chlorophyll synthesis and chloroplast biogenesis, which, in turn, may lead to changes in the resistance of plants to light-induced stress.

The basidiomycete Lentinus tigrinus was cultured in media containing copper ions added at different growth stages. Copper ions at increased concentrations decelerated of the fungal biomass accumulation. The later Cu2+ ions were added, the better the fungal mycelium developed, and the toxic effect of Cu2+ was less pronounced. The maximum laccase activity (47 U/ml) was observed in the presence of 1.5-2.0 mM Cu2+ added on day 4 of cultivation.