Photosensitizing effects and physicochemical properties of chlorophyll a derivatives with hydrophilic oligoethylene glycol fragments at the macrocycle periphery.

In this work, screening studies of the cytotoxic effect of chlorins with fragments of di-, tri-, and pentaethylene glycol at the macrocycle periphery in relation to HeLa, A549, and HT29 cells were performed. It is shown that, despite different hydrophobicity, all the compounds studied have a comparable photodynamic effect. The conjugate of chlorin e6 with pentaethylene glycol, which has the lowest tendency to association among the studied compounds with tropism for low density lipoproteins and the best characteristics of the formation of molecular complexes with Tween 80, has a significant difference in dark and photoinduced toxicity (ratio IC50(dark)/IC50(photo) approximately 2 orders of magnitude for all cell lines), which allows to hope for a sufficiently large "therapeutic window". A study of the interaction of this compound with HeLa cells shows that the substance penetrates the cell and, after red light irradiation induces ROS appearance inside the cell, associated, apparently, with the photogeneration of singlet oxygen. These data indicate that photoinduced toxic effects are caused by damage to intracellular structures as a result of oxidative stress. Programmed type of cell death characterized with caspase-3 induction is prevailing. So, the conjugate of chlorin e6 with pentaethylene glycol is a promising antitumor PS that can be successfully solubilized with Tween 80, which makes it suitable for further in vivo studies.

Systematic review of comparative transcriptomic studies of cellular resistance to genotoxic stress.

The development of resistance by tumor cells to various types of therapy is a significant problem that decreases the effectiveness of oncology treatments. For more than two decades, comparative transcriptomic studies of tumor cells with different sensitivities to ionizing radiation and chemotherapeutic agents have been conducted in order to identify the causes and mechanisms underlying this phenomenon. However, the results of such studies have little in common and often contradict each other. We have assumed that a systematic analysis of a large number of such studies will provide new knowledge about the mechanisms of development of therapeutic resistance in tumor cells. Our comparison of 123 differentially expressed gene (DEG) lists published in 98 papers suggests a very low degree of consistency between the study results. Grouping the data by type of genotoxic agent and tumor type did not increase the similarity. The most frequently overexpressed genes were found to be those encoding the transport protein ABCB1 and the antiviral defense protein IFITM1. We put forward a hypothesis that the role played by the overexpression of the latter in the development of resistance may be associated not only with the stimulation of proliferation, but also with the limitation of exosomal communication and, as a result, with a decrease in the bystander effect. Among down regulated DEGs, BNIP3 was observed most frequently. The expression of BNIP3, together with BNIP3L, is often suppressed in cells resistant to non-platinum genotoxic chemotherapeutic agents, whereas it is increased in cells resistant to ionizing radiation. These observations are likely to be mediated by the binary effects of these gene products on survival, and regulation of apoptosis and autophagy. The combined data also show that even such obvious mechanisms as inhibition of apoptosis and increase of proliferation are not universal but show multidirectional changes.

Soil microbiota and microarthropod communities in oil contaminated sites in the European Subarctic.

The present comprehensive study aimed to estimate the aftermath of oil contamination and the efficacy of removing the upper level of polluted soil under the conditions of the extreme northern taiga of northeastern European Russia. Soil samples from three sites were studied. Two sites were contaminated with the contents of a nearby sludge collector five years prior to sampling. The highly contaminated upper soil level was removed from one of them. The other was left for self-restoration. A chemical analysis of the soils was conducted, and changes in the composition of the soil zoocoenosis and bacterial and fungal microbiota were investigated. At both contaminated sites, a decrease in the abundance and taxonomic diversity of indicator groups of soil fauna, oribatid mites and collembolans compared to the background site were found. The pioneer eurytopic species Oppiella nova, Proisotoma minima and Xenyllodes armatus formed the basis of the microarthropod populations in the contaminated soil. A complete change in the composition of dominant taxonomic units was observed in the microbiota, both the bacterial and fungal communities. There was an increase in the proportion of representatives of Proteobacteria and Actinobacteria in polluted soils compared to the background community. Hydrocarbon-degrading bacteria-Alcanivorax, Rhodanobacter ginsengisoli, Acidobacterium capsulatum, and Acidocella-and fungi-Amorphotheca resinae abundances greatly increased in oil-contaminated soil. Moreover, among both bacteria and fungi, a sharp increase in the abundance of uncultivated organisms that deserve additional attention as potential oil degraders or organisms with a high resistance to oil contamination were observed. The removal of the upper soil level was partly effective in terms of decreasing the oil product concentration (from approximately 21 to 2.6 g/kg of soil) and preventing a decrease in taxonomic richness but did not prevent alterations in the composition of the microbiota or zoocoenosis.

[Cytogenetic effects in Allium schoenoprasum growing on the anthropogenically contaminated soil].

Cytogenetic effects in Allium schoenoprasum meristematic root tip cells grown for a year on the territory contaminated with 235U, 238U and 232Th decay series radionuclides, heavy metals and As were studied. The area is characterized with different concentrations of chemical compounds in soil affecting a toxic element migration in biocoenosis. Analysis of the chromosome aberration spectrum showed an ambiguous cell response to soil contamination. Within the weighted absorbed dose range up to 1.2 Gy the higher the dose the aberrant cell frequency increase was shown. But further increase in the dose resulted in a genotoxic effect decrease due to high toxic effects of heavy metals and radionuclides in soil. This was registered as a mitotic index decrease that can provoke a chromosome aberration frequency underestimation and result in erroneous conclusions about genotoxic effects in A. schoenoprasum used as a bioindicator.

[The level of DNA damage and DNA reparation rate in cells of earthworms sampled from natural populations for numerous generations inhabited territories with anthropogenically enhanced levels of radionuclides in soil].

Low doses of ionizing radiation and chemical toxic agent effects on biological systems on different organization levels have been studied by numerous researchers. But there is a clear lack of experimental data that allow one to reveal molecular and cellular adaptations of plants and animals from natural populations to adverse effects of environmental factors. The present study was aimed to assess genotoxic effects in earthworms Aporrectodea caliginosa Savigny and Lumbricus rubellus Hoffmeister sampled from the populations that during numerous generations inhabited the territories with a technogeneously enhanced content of natural origin radionuclides and heavy metals in soil. The levels ofthe DNA damage detected with alkaline and neutral versions of Comet-assay in invertebrates from contaminated territories were established not to differ from the spontaneous level found in the animals from the reference population. At the same time the rate of the DNA damage reparation induced in A. caliginosa sampled from the contaminated sites with additional acute γ-irradiation (4 Gy) was found to be considerably higher as compared with earthworms from the reference population.

[Radiation risk assessment for plant reference species (Pinus sylvestris and Vicia cracca) from the area of radium production waste storage].

The risk of an enhanced level of radionuclides of the uranium and thorium decay series in the environment for reference plant species (Pinus sylvestris and Vicia cracca) was assessed. 238U, 230Th, 226Ra, 210Po, 232Th and 228Th concentration factors for plants were found to be lower than one. The aboveground parts of Vicia cracca sampled from the area of the radium production waste storage mainly accumulated 22Ra, Pinus sylvestris branches--210Pb, 226Ra and 210Po. LOEDR calculated for the chromosome aberration frequency in both plant studies was 17-71 microGy/h. LOERD values for the reproductive capacity decrease in P. sylvestris and V. cracca were 17-71 microGy/h and 116-258 microGy/h, correspondingly. EDR10 for the chromosome aberration frequency in P. sylvestris and V. cracca were 148 and 347 microGy/h, that is, correspondingly, 255 and 708 times higher that background values. EDR10 for the plant reproductive capacity was 11-34 microGy/h, which 19-69 times increases the background values.

[Regularities of lateral distribution of uranium and thorium decay series radionuclides in the anthropogenically changed soils from the area of radium production waste storage].

Cartographical investigations of the territory of radium production waste storage has shown some changes in lateral differentiation of radionuclides of uranium and thorium decay series to occur during 27 years (1981-2008). Those changes are caused mostly by flat denudation typical for fluvial terrace. At present radionuclides of uranium and thorium decay series are concentrated mostly in flood lands and relief depressions. At the same time, decrease in the radionuclide activity concentration in 0-20 cm soil layer is observed with changes in lateral distribution. Total stocks of 226Ra, 210Pb and 210Po within catena soils studied in the northern and southern parts of the waste storage decreased 3-6 times, 238U - 2 times, and did not significantly change in case of 232Th during 27 years. Nonetheless, most of the samples studied are referred to radioactive waste both according to Russian standards (SPORO-2002) and IAEA safety norms (IAEA, 2004).

[Assessment of soil degradation in regions of nuclear power explosions at Semipalatinsk Nuclear Test Site].

Degree of the soil cover degradation at the "Balapan" and "Experimental field" test sites was assessed based on Allium-test of soil toxicity results and international guidelines on radioactive restriction of solid materials (IAEA, 2004) and environment (Smith, 2005). Soil cover degradation maps of large-scale (1 : 25000) were made. The main part of the area mapped belongs to high-contaminated toxic degraded soil. A relationship between the soil toxicity and the total radionuclide activity concentrations was found to be described by power functions. When the calculated value (equal to 413-415 Bq/kg of air dry soil) increases, the soil becomes toxic for plants. This value is 7.8 times higher than the maximal value for background territories (53 Bq/kg) surrounding SNTS. Russian sanitary and hygienic guidelines (Radiation safety norms, 2009; Sanitary regulations of radioactive waste management, 2003) underestimate the degree of soil radioactive contamination for plants.

[The assessment of no adverse effect doses for plant populations chronically exposed to radionuclides of uranium and thorium decay series].

Dose rates cause no adverse effects on natural populations of Pinus sylvestris L. and Vicia cracca L. inhabiting territories contaminated by uranium mill tailings and radium production wastes (Vodny settlement, Komi Republic) were determined. A significant increase in embryonic lethal mutation frequency in V. cracca legumes and decrease in seedlings survival rate as compared with control values were registered at dose rate equal to 1.67 mGy/day, that is 280 times higher than the one calculated for the reference site. The adverse effects in P. sylvestris expressed in increased frequency of chromosome aberrations in meristematic root tips and decreased reproductive capacity of seeds were determined at absorbed dose rate equal to 0.083 mGy/day. Data obtained show that the decrease in plant reproductive capacity in case of chronic exposure of radionuclides of uranium and thorium decay series can observe at lower weighted absorbed dose rates than in case of environmental contamination by artificial radionuclides.

[The assessment of radionuclide contamination and toxicity of soils sampled from "experimental field" site of Semipalatinsk nuclear test site].

Large-scale maps (1:25000) of soil contamination with radionuclides, lateral distribution of 137Cs, 90Sr, Fe and Mn water-soluble compounds and soil toxicity in "Experimental field" site of Semipalatinsk nuclear test site were charted. At present soils from studied site (4 km2) according to basic sanitary standards of radiation safety adopted in Russian Federation (OSPORB) do not attributed to radioactive wastes with respect to data on artificial radionuclide concentration, but they do in compliance with IAEA safety guide. The soils studied can not be released from regulatory control due to radioactive decay of 137Cs and 90Sr and accumulation-decay of 241Am up to 2106 year according to IAEA concept of exclusion, exemption and clearance. Data on bioassay "increase of Chlorella vulgaris Beijer biomass production in aqueous extract from soils" show that the largest part of soils from the studied site (74%) belongs to stimulating or insignificantly influencing on the algae reproduction due to water-soluble compounds effect. Toxic soils occupy 26% of the territory. The main factors effecting the algae reproduction in the aqueous extracts from soil are Fe concentration and 90Sr specific activity: 90Sr inhibits but Fe stimulates algae biomass production.

[Assessment of modern radioecological situation at nuclear explosion "Chagan" (Balapan Site, Semipalatinsk Nuclear Test Site, Kazakhstan)].

Results on estimation of modern radioecological situation at nuclear explosion "Chagan" based on large-scale cartographic studies (1:25000) of a test area (4 km2) are presented. Maximum gamma-irradiation doses were observed at bulk of ground surrounded a crater and at radioactive fall-outs extended to the North-East and to the SouthWest from the crater. Based on data on artificial radionuclide specific activity most part of soil samples were attributed to radioactive wastes according to IAEA (1996) and OSPORB (1999). Natural decrease of soil radioactivity up to safety level due to 60Co, 137Cs, 90Sr, 152Eu, 154Eu radioactive decay and 241Am accumulation-decay will not take place within the next 60 years at the studied area.

[The estimation of ionizing irradiation impact on Vicia cracca cenopopulations growing on the territory contaminated with the wastes of radium production].

The radiation exposure on cenopopulations Vicea cracca L. growing on the territory contaminated with the wastes of radium production was estimated. The relationship between the chromosome aberration in seedlings root tip cells and irradiation dose was found to be linear. The significant cytogenetic effects in chronically irradiated Vicia cracca cenopopulation are observed at doses (equal to 0.006-0.7 Gy) 10 times upward the natural radiation background level. The reduced reproductive success (significantly increased embryonic lethal mutation level) is observed at weighted absorbed doses (equal to 0.2-0.7 Gy) up to 200-700 times higher than the natural radiation background level. It is showh, that the radiation hygienic standards of permissible exposure are noticeably stricter that the radioecological limits.

[The mechanisms of 232Th and of Ce (III) toxic action on Chlorella vulgaris Beijer. Estimation of 232Th radiation impact contribution into toxic effect induced].

232Th and Ce (III) toxic effects and its modifications with caffeine and D,L-buthionine-(S,R)-sulphoximine on Chlorella vulgaris Beijer were studied using an optical density measure after 24 hours growth. Concentrations of 232Th or of Ce--toxic effect relationship were shown to be nonlinear. In the first (nontoxic) concentration range (for Ce 0.036-1.642 micromol/L and for 232Th 0.001-1.551 micromol/L) algae biomass production registered by optical density do not significantly differ from the control one. In the second (toxic) concentration range dose-effect relationship for 232Th is characterized with quadratic dependence and in the case of Ce--with exponential dependence. 232Th radiation component contribution into effect observed is appeared as induction of DNA damages additional to spontaneous at the radionuclide concentration (equal to 0.345 micromol/L) that is three times lower than in case of the non-radioactive chemical analog Ce (1.071 micromol/L).

[Quantitative estimation combined chemical and radioactive exposure on biological objects].

We summarized the researches to estimate the methods of combined (chemical and/or radioactive nature) factor action on biological objects. The data examined indicate that methods commonly used need a revision and adaptation in case of analyzing data on biological effects in natural plant and animal populations. Basic principles of evaluation of man-caused factor contribution into variation level observed in natural population are discussed.

[Genetic variance in Vicia cracca cenopopulation inhabiting site with enhanced level of natural radioactivity].

The contribution of low dose rate ionizing radiation into genetic variance in Vicia cracca L. cenopopulation inhabiting high natural background territories more then 40 years quantity estimation was made. Incorporated in the aboveground parts of Vicia cracca 230Th determine both the level of intrapopulation genetic variance and the adaptive possibility. Significantly increased frequency of double fragments was revealed in root tips of plants inhabiting all experimental plots. This type of damages depends on 226Ra concentrations accumulated in the aboveground parts of Vicia cracca. External irradiation influences the embryonic lethals. It was found that the relative contribution on mutagenesis induced by ionizing radiation was significant and was about 3-5% of the total variance.

[The influence of cadmium and potassium on the level of cytogenetic effects induced by thorium-232 in Allium cepa root meristem].

The influence of different concentrations of cadmium and potassium on the levels of mutagenic and cytotoxic effects induced by thallium-232 in Allium cepa root meristem has been studied. The combined action of 232Th (0.8 microM) with cadmium in non-toxic (0.009 microM) and toxic (5 microM) concentrations resulted in sinergetic increase of the frequency of aberrant cells in Allium cepa root meristem. Decrease of the mutagenic effect to the additive level and antagonism with respect to the cytotoxic one was observed only at the certain concentrations of 232Th (0.8 microM) and Cd (0.09 microM) and the time of impact 30 h. In contrast to the heavy metal cadmium the essential for plants potassium at all studied concentrations (0.008, 6, 13 mM) decreased the number of cytogenetic aberrations in control experiments and under the effect of 232Th. The maximum protective effect of potassium was detected at the concentration 13 mM.

[Mechanisms of 232Th effects on Chlorella vulgaris Beljer and modifications of it's toxic effect with caffeine and buthionine sulfoximine].

232Th effects and its modifications with caffeine and D, L-buthionine-(S, R)-sulphoximine in Chlorella vulgaris Beijer cells was studied with use an optical density measure after 24 hours growth. Was shown relationship between concentration and toxic effect that is nonlinear and characterized with three parts different in induced damages level. In the first concentration range (0.001-1.551 micromol/l) chlorella growth parameters don't significantly differ from control ones. In the second one (1.724-3.017 micromol/1) statistically significant increase of optical density is but the effect does not dependent on 232Th concentration. The 232Th concentration (>3.448 micromol/l) increase the monotonous decrease in optical density was observed. The main role in 232Th toxic effect decrease make processes of DNA reparation, but not free radical scavenging with glutathione.

[Toxic and cytogenetic effects induced in Allium cepa with low concenrations of Cd and 232th].

232Th (7.76 x 10(-7) M) and Cd (0.89 x 10(-8) M) in concentrations which do not exceed officially prescribed standards when entering with water do not increase the frequency of chromosome aberrations in comparison with the control. Such concentrations do not cause toxic effects in plants on the levels of tissues and of the whole organism but they do display their activity on the cell level damaging division spindle. Dependence "cadmium concentration-effect" is not linear for any type of cytogenetical damages. At the concentration of cadmium 0.89 x 10(-7) M its influence on formation of division spindle is weakened and the frequency of chromosome aberrations is reducing in comparison with the control and with the effects induced at lower concentrations of cadmium in solution (0.89 x 10(-8) M). Cadmium in high concentration (5.34 x 10(-5) M) causes significant toxic and mutagenic effects.