No abstract

No abstract

Blooms of cyanobacteria have been documented throughout history, all over the world. Mass populations of these organisms typically present hazards to human health and are known for the production of a wide range of highly toxic metabolites-cyanotoxins, of which among the most common and most investigated are the microcystins. The toxicity of the family of microcystin congeners to animal and cell models has received much attention; however, less is known about their negative effects on human health, whether via acute or chronic exposure. Useful information may be acquired through epidemiological studies since they can contribute to knowledge of the relationships between cyanotoxins and human health in environmental settings. The aim of this review is to compile and evaluate the available published reports and epidemiological investigations of human health incidents associated with exposure to mass populations of cyanobacteria from throughout the world and to identify the occurrence and likely role of microcystins in these events. After an initial screening of 134 publications, 42 publications (25 on the chronic and 17 on the acute effects of cyanotoxins) describing 33 cases of poisonings by cyanobacterial toxins in 11 countries were reviewed. The countries were Australia, China, Sri Lanka, Namibia, Serbia, Sweden, UK, Portugal, Brazil, USA, and Canada. At least 36 publications link cyanobacteria/cyanotoxins including microcystins to adverse human health effects. The studies were published between 1960 and 2016. Although the scattered epidemiological evidence does not provide a definitive conclusion, it can serve as additional information for the medical assessment of the role of microcystins in cancer development and other human health problems. This paper discusses the major cases of cyanotoxin poisonings as well as the strengths, weaknesses, and importance of the performed epidemiological research. This study also proposes some recommendations for future epidemiological work.

In non-Western civilizations, cyanobacteria have been part of the human diet for centuries. Today, microalgae and cyanobacteria are either produced in controlled cultivation processes or harvested from the natural habitats and marketed as food supplements around the world. Cyanobacteria produce a vast array of different biologically active compounds, some of which are expected to be used in drug development. The fact that some of the active components from cyanobacteria potentially have anticancer, antimicrobial, antiviral, anti-inflammatory, and other effects is being used for marketing purposes. However, introduction of these products in the form of whole biomass for alimentary purposes raises concerns regarding the potential toxicity and long-term effects on human health. Here, we review data on the use of cyanobacteria and microalgae in human nutrition and searched for available information on legislature that regulates the use of these products. We have found that, although the quality control of these products is most often self-regulated by the manufacturers, different governmental agencies are introducing strict regulations for placing novel products, such as algae and cyanobacteria, on the market. The existing regulations require these products to be tested for the presence of toxins, such as microcystin; however, other, sometimes novel, toxins remain undetected, and their long-term effects on human health remain unknown.

A large part of Central Serbia experiences continual shortage of sufficient ground water resources. For that reason, more than 20 reservoirs serve as drinking water suppliers. Significant and persistent cyanobacterial "blooms" have been recognized in nine of them. Samples for cyanotoxin analyses were taken during and after "blooms" in Celije Reservoir and from Krusevac town-supplied tap water from that reservoir two days later. Concentration of microcystin-LR was 650 microg L(-1) in the reservoir, while the tap water contained 2.5 microg L(-1). In the two investigated periods, the high primary liver cancer (PLC) mortality of 11.6 from 1980-1990 and extremely high PLC incidence of 34.7 from 2000-2002 were observed in the regions affected by heavy cyanobacterial "blooms." In contrast, PLC mortality and incidence rates were substantially lower in the regions not affected by cyanobacterial blooms: in 1980-1990 the rate of PLC mortality amounted to 2.7 in Kosovo, 7.6 in Vojvodina, and 8.3 in the non-affected regions of Central Serbia; while in 2000-2002 PLC incidence amounted to 4.1 in Kosovo, 5.2 in Vojvodina, and 13.6 in the non- or less-affected regions of Central Serbia. Keeping in mind that the most affected PLC regions in Central Serbia (Toplicki, Niski, and Sumadijski regions) have the water supply systems based on six reservoirs found regularly in bloom during summer months and that some of the regions are also connected with two boundary "blooming" reservoirs, representing a total of eight of nine blooming reservoirs, it is easy to presume that the PLC incidence could be related to drinking water quality. The uneven geographic distribution of liver cancer in Serbia is conspicuous and hot spots could be related to drinking water supply. It is very clear that the high-risk regions for PLC occurrence correspond with drinking water reservoirs continually found with cyanobacterial blooms, and the low risk regions correspond with water supplies not affected by cyanobacteria.

It is known that microcystin (MC) is a cyanotoxin that is a potent environmental inhibitor of eucariotic protein serine/threonine phosphatase 1 and 2A, both in vitro and in vivo. Consequently, these cyanobacterial toxins (MC-IARC group 2B carcinogen, MC extracts-group 3) are potent tumor promoters and there is an indication that they may also act as tumor initiators. The ability of microcystin-LR (MC-LR) to act as a tumor initiator is based on fact that it can induce DNA damage either by direct interaction with DNA or by indirect mechanisms through formation of reactive oxygen species (ROS). Both acute and chronic exposures, to either low or high doses of MC-LR, can activate apoptotic pathways. Chronic exposure to low concentrations of MC-LR contributes to increased risk for cancer development. Epidemiological studies, in certain areas of China, have suggested that MC is one of the risk factors for the high incidence of primary liver cancer (PLC). Recently, we have reported a correlation between PLC and cyanobacterial "blooms" in reservoirs used as a source for drinking water supply in central Serbia. It appears that the combination of acute and chronic exposures to both high and low doses of MC can lead to PLC initiation and promotion. Based on this, we propose that the requirement for the co-factors such as aflatoxin B1 and other mycotoxins, HBV, HCV, alcohol, etc. is not needed for initiation and promotion of PLC by MC-LR as was suggested earlier. The possible mechanisms of the genotoxicity of MC and its role as a hepatocarcinogen are outlined in this review. Furthermore, we show that the exposure of hepatocytes to MC can lead either to malignant proliferation or apoptosis.

Loess-palaeosol sequences are valuable archives of past environmental changes. Although regional palaeoclimatic trends and conditions in Southeastern Europe have been inferred from loess sequences, large scale forcing mechanisms responsible for their formation have yet to be determined. Southeastern Europe is a climatically sensitive region, existing under the strong influence of both Mediterranean and continental climates. Establishment of the spatial and temporal evolution and interaction of these climatic areas is essential to understand the mechanisms of loess formation. Here we present high-resolution grain-size, environmental magnetic, spectrophotometric and geochemical data from the Stalać section in the Central Balkans (Serbia) for the past ~350,000 years. The goal of this study is to determine the influence of the Mediterranean climate during this period. Data show that the Central Balkans were under different atmospheric circulation regimes, especially during Marine Isotope Stages 9 and 7, while continental climate prevailed further north. We observe a general weakening of the Mediterranean climate influence with time. Our data suggest that Marine Isotope Stage 5 was the first interglacial in the Central Balkans that had continental climate characteristics. This prominent shift in climatic conditions resulted in unexpectedly warm and humid conditions during the last glacial.

Loess deposits in the Vojvodina region, northern Serbia, are among the oldest and most complete loess-paleosol sequences in Europe to date. These thick sequences contain a detailed paleoclimatic record from the late Early Pleistocene. Based on the correlation of detailed magnetic susceptibility (MS) records from Vojvodina with the Chinese loess record and deep-sea isotope stratigraphy we here reconfirm and expand on a stratigraphic model of the Vojvodinian loess-paleosol chronostratigraphic sequence following the Chinese loess stratigraphic system.Variations in MS, dust accumulation rates, and the intensity of pedogenesis demonstrate evidence for a Middle Pleistocene climatic and environmental transition. The onset of loess deposition in Vojvodina also indicates a direct link between dust generation in Europe and that in the interior of Eurasia since the Early Pleistocene. The youngest part of the Early Pleistocene and oldest part of the Middle Pleistocene is characterised by relatively uniform dust accumulation and soil formation rates as well as relatively high magnetic susceptibility values. In contrast, the last five interglacial-glacial cycles are characterised by sharp environmental differences between high dust accumulation rates during the glacials and low rates observed during soil development. The data presented in this study demonstrate the great potential of Vovjodina's loess archives for accurate reconstruction of continental Eurasian Pleistocene climatic and environmental evolution.