Genotoxic potential of selected cytostatic drugs in human and zebrafish cells

Due to their increasing use, the residues of anti-neoplastic drugs have become emerging pollutants in aquatic environments. Most of them directly or indirectly interfere with the cell’s genome, which classifies them into a group of particularly dangerous compounds. The aim of the present study was to conduct a comparative in vitro toxicological characterisation of three commonly used cytostatics with different mechanisms of action (5-fluorouracil [5-FU], cisplatin [CDDP] and etoposide [ET]) towards zebrafish liver (ZFL) cell line, human hepatoma (HepG2) cells and human peripheral blood lymphocytes (HPBLs). Cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and acridine orange/ethidium bromide staining. All three drugs induced time- and dose-dependent decreases in cell viability. The sensitivity of ZFL and HepG2 cells towards the cytotoxicity of 5-FU was comparable (half maximal inhibitory concentration (IC₅₀) 5.3 to 10.4 μg/mL). ZFL cells were more sensitive towards ET- (IC₅₀ 0.4 μg/mL) and HepG2 towards CDDP- (IC₅₀ 1.4 μg/mL) induced cytotoxicity. Genotoxicity was determined by comet assay and cytokinesis block micronucleus (CBMN) assay. ZFL cells were the most sensitive, and HPBLs were the least sensitive. In ZFL cells, induction of DNA strand breaks was a more sensitive genotoxicity endpoint than micronuclei (MNi) induction; the lowest effective concentration (LOEC) for DNA strand break induction was 0.001 μg/mL for ET, 0.01 μg/mL for 5-FU and 0.1 μg/mL for CDDP. In HepG2 cells, MNi induction was a more sensitive genotoxicity endpoint. The LOEC values were 0.01 μg/mL for ET, 0.1 μg/mL for 5-FU and 1 μg/mL for CDDP. The higher sensitivity of ZFL cells to cytostatic drugs raises the question of the impact of such compounds in aquatic ecosystem. Since little is known on the effect of such drugs on aquatic organisms, our results demonstrate that ZFL cells provide a relevant and sensitive tool to screen genotoxic potential of environmental pollutant in the frame of hazard assessment.     

Declining coastal piscivore populations in the Baltic Sea: Where and when do sticklebacks matter?

Intraguild predation interactions make fish communities prone to exhibit alternative stable states with either piscivore or prey fish dominance. In the Baltic Sea, local declines of coastal piscivores like perch (Perca fluviatilis) have been observed to coincide with high densities of sticklebacks (Gasterosteus aculeatus). Mechanisms behind this shift between piscivore and stickleback dominance were studied both experimentally and in field. Results showed that predation by sticklebacks has a strong negative effect on perch larvae survival, but this effect rapidly decreases with increasing perch size, likely due to gape limitations and digestion constraints in sticklebacks. Large spatial and temporal variations in patterns of stickleback migration into perch spawning sites were observed. Whether or not high density of sticklebacks will cause declines in coastal piscivore populations is suggested to depend on the availability of spawning sites in which sticklebacks do not migrate into or arrive late in the reproduction season of coastal piscivores.     

Metal leaching from MSWI bottom ash as affected by salt or dissolved organic matter

In order to manage municipal solid waste incineration (MSWI) bottom ash safely, risk assessments, including the prediction of leaching under different field conditions, are necessary. In this study, the influence of salt or dissolved organic matter (DOM) in the influent on metal leaching from MSWI bottom ash was investigated in a column experiment. The presence of salt (0.1M NaCl) resulted in a small increase of As leaching, whereas no impact on leachate concentration was found when lakewater DOM (35.1mg/l dissolved organic carbon) was added. Most of the added DOM was retained within the material. Further, X-ray spectroscopy revealed that Cu(II) was the dominating form of Cu and that it probably occurred as a CuO-type mineral. The Cu(2+) activity in the MSWI bottom ash leachate was most likely determined by the dissolution of CuO together with the formation of Cu-DOM complexes and possibly also by adsorption to (hydr)oxide minerals. The addition of lake DOM in the influent resulted in lower saturation indices for CuO in the leachates, which may be due to slow CuO dissolution kinetics in combination with strong Cu-DOM complexation.     

Opportunities and Challenges to Capturing the Multiple Potential Benefits of REDD+ in a Traditional Transnational Savanna-Woodland Region in West Africa

The REDD+ scheme of the United Nations intends to offer developing countries financial incentives to reduce the rates of deforestation and forest degradation for reducing global CO₂ emissions. This is combined with building carbon stocks in existing wooded ecosystems and fostering other soil, biodiversity and water conservation objectives. Successful application of REDD+ to the Xylophone Triangle of West Africa faces substantial challenges and risks to both meeting REDD+ objectives and to the local people’s rights and livelihoods. The transnationality of the culturally coherent area requires collaboration of three national governments. The opportunities, however, are great to capitalize on the region’s biodiversity, the well-developed traditional ecological knowledge and the use of local medicinal plants as an integral part of the agro-ecosystem. Possibilities open to, not only sequester carbon, but also to increase the resilience of the ecosystem and of independent rural livelihoods in the face of climate change and globalization.     

Use of sensitive methods for detection of DNA damage on human lymphocytes exposed to p,p′-DDT: Comet assay and new criteria for scoring micronucleus test

Wide distribution, stability and long persistence in the environment of dichlorodiphenyltrichloroethane (DDT), probably the best-known and most useful insecticide in the world, imposes the need for further examination of the effect of this chemical on human health and especially on the human genome. In this study, peripheral blood human lymphocytes from a healthy donor were exposed to 0.025 mg/L concentration of p,p′-DDT at different time periods (1, 2, 24 and 48 h). For the assessment of genotoxic effect, the new criteria for scoring micronucleus test and alkaline comet assay were used. Both methods showed that p,p′-DDT induces DNA damage in low concentration used in this research. Results of micronucleus test showed a statistically significant (p < 0.05) genotoxic effect of p,p′-DDT on human lymphocytes compared with corresponding control and a different exposure time. A comet assay also showed increased DNA damage caused in p,p′-DDT-exposed human lymphocytes than in corresponding control cells for the tail length. Results obtained by measuring the level of DNA migration and incidence of micronuclei (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) indicate the sensitivity of these tests and their application in detection of primary genome damage after long-term exposure to establish the effect of p,p′-DDT on human genome.     

Toxicity of mancozeb,chlorothalonil, captan,fluopyram, boscalid,and difenoconazole to Didymella applanata isolates from Serbia

Field isolates of Didymella applanata, the causal agent of spur blight of raspberry, were evaluated in vitro for their sensitivity to mancozeb, chlorothalonil, captan, fluopyram, boscalid and difenoconazole. A total of 10 isolates, collected during 2013 at five localities in the major raspberry growing region in Serbia, and characterized as copper hydroxide, dithianon, and tebuconazole (sensitive), pyraclostrobin (sensitive or highly resistant) and fluazinam (sensitive or moderately resistant), were used in this study. The EC₅₀ values for the isolates ranged from 1.33 to 2.88 mg L^?1 for mancozeb, from 3.18 to 6.65 mg L^?1 for chlorothalonil, from 15.75 to 24.69 mg L^?1 for captan and from 1.80 to 8.20 mg L^?1 for fluopyram. The narrowest range of EC₅₀ values was recorded for difenoconazole (0.23–0.49 mg L^?1), whereas the widest range was obtained for boscalid (4.49–49.25 mg L^?1). The calculated resistance factors showed that all D. applanata isolates were sensitive to mancozeb, chlorothalonil, captan, and difenoconazole. Four isolates were moderately resistant to boscalid, while three of them were also moderately resistant to fluopyram. This finding of moderately resistant isolates to these SDHI fungicides indicates a possible cross-resistance which should be clarified in further investigations.     

Alteration of cholinesterase activity as possible mechanism of silver nanoparticle toxicity

Due to their broad-spectrum antimicrobial activity, silver nanoparticles (AgNPs) have been used in a large number of commercial and medical products. Such proliferated AgNP production poses toxicological and environmental issues which need to be addressed. The present study aimed to investigate the effects of AgNPs on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), important enzymes in areas of neurobiology, toxicology and pharmacology. Three different AgNPs, prepared by the chemical reduction using trisodium citrate, hydroxylamine hydrochloride (Cl-AgNPs), and borohydride following stabilization with poly(vinyl alcohol), were purified and characterised with respect to their sizes, shapes and optical properties. Their inhibition potential on AChE and BChE was evaluated in vitro using an enzyme assay with o-nitrophenyl acetate or o-nitrophenyl butyrate as substrates, respectively. All three studied AgNPs were reversible inhibitors of ChEs. Among tested nanoparticles, Cl-AgNP was found to be the most potent inhibitor of both AChE and BChE. Although the detailed mechanism by which the AgNPs inhibit esterase activities remains unknown, structural perturbation of the enzyme may be the common mode of ChE inhibition by AgNPs.     

Planetary Stewardship in an Urbanizing World: Beyond City Limits

Cities are rapidly increasing in importance as a major factor shaping the Earth system, and therefore, must take corresponding responsibility. With currently over half the world’s population, cities are supported by resources originating from primarily rural regions often located around the world far distant from the urban loci of use. The sustainability of a city can no longer be considered in isolation from the sustainability of human and natural resources it uses from proximal or distant regions, or the combined resource use and impacts of cities globally. The world’s multiple and complex environmental and social challenges require interconnected solutions and coordinated governance approaches to planetary stewardship. We suggest that a key component of planetary stewardship is a global system of cities that develop sustainable processes and policies in concert with its non-urban areas. The potential for cities to cooperate as a system and with rural connectivity could increase their capacity to effect change and foster stewardship at the planetary scale and also increase their resource security.     

Structuring sustainability science

It is urgent in science and society to address climate change and other sustainability challenges such as biodiversity loss, deforestation, depletion of marine fish stocks, global ill-health, land degradation, land use change and water scarcity. Sustainability science (SS) is an attempt to bridge the natural and social sciences for seeking creative solutions to these complex challenges. In this article, we propose a research agenda that advances the methodological and theoretical understanding of what SS can be, how it can be pursued and what it can contribute. The key focus is on knowledge structuring. For that purpose, we designed a generic research platform organised as a three-dimensional matrix comprising three components: core themes (scientific understanding, sustainability goals, sustainability pathways); cross-cutting critical and problem-solving approaches; and any combination of the sustainability challenges above. As an example, we insert four sustainability challenges into the matrix (biodiversity loss, climate change, land use changes, water scarcity). Based on the matrix with the four challenges, we discuss three issues for advancing theory and methodology in SS: how new synergies across natural and social sciences can be created; how integrated theories for understanding and responding to complex sustainability issues can be developed; and how theories and concepts in economics, gender studies, geography, political science and sociology can be applied in SS. The generic research platform serves to structure and create new knowledge in SS and is a tool for exploring any set of sustainability challenges. The combined critical and problem-solving approach is essential.