Microcystins are toxins produced by freshwater cyanobacteria. They are cyclic heptapeptides that exhibit hepato-and neurotoxicity. However, the transport systems that mediate uptake of microcystins into hepatocytes and across the blood-brain barrier have not yet been identified. Using the Xenopus laevis oocyte expression system we tested whether members of the organic anion transporting polypeptide superfamily (rodent: Oatps; human: OATPs) are involved in transport of the most common microcystin variant microcystin-LR by measuring uptake of a radiolabeled derivative dihydromicrocystin-LR. Among the tested Oatps/OATPs, rat Oatp1b2, human OATP1B1, human OATP1B3, and human OATP1A2 transported microcystin-LR 2-to 5-fold above water-injected control oocytes. This microcystin-LR transport was inhibited by co-incubation with the known Oatp/OATP substrates taurocholate (TC) and bromosulfophthalein (BSP). Microcystin-LR transport mediated by the human OATPs was further characterized and showed saturability with increasing microcystin-LR concentrations. The apparent K m values amounted to 7 F 3 AM for OATP1B1, 9 F 3 AM for OATP1B3, and 20 F 8 AM for OATP1A2. No microcystin-LR transport was observed in oocytes expressing Oatp1a1, Oatp1a4, and OATP2B1. These results may explain some of the observed organ-specific toxicity of microcystin-LR. Oatp1b2, OATP1B1, and OATP1B3 are responsible for microcystin transport into hepatocytes, whereas OATP1A2 mediates microcystin-LR transport across the blood-brain barrier.

The mycotoxin ochratoxin A (OTA) has been linked to the genesis of several disease states in both animals and humans. It has been described as nephrotoxic, carcinogenic, teratogenic, immunotoxic, and hepatotoxic in laboratory and domestic animals, as well as being thought to be the probable causal agent in the development of nephropathies (Balkan Endemic Nephropathy, BEN and Chronic Interstitial Nephropathy, CIN) and urothelial tumors in humans. As a result, several international agencies are currently attempting to define safe legal limits for OTA concentration in foodstuffs (e.g., grain, meat, wine, and coffee), in processed foods, and in animal fodder. In order to achieve this goal, an accurate risk assessment of OTA toxicity including mechanistic and epidemiological studies must be carried out. Ochratoxin has been suggested by various researchers to mediate its toxic effects via induction of apoptosis, disruption of mitochondrial respiration and/or the cytoskeleton, or, indeed, via the generation of DNA adducts. Thus, it is still unclear if the predominant mechanism is of a genotoxic or an epigenetic nature. One aspect that is clear, however, is that the toxicity of OTA is subject to and characterized by large species-and sex-specific differences, as well as an apparently strict structure-activity relationship. These considerations could be crucial in the investigation of OTA-mediated toxicity. Furthermore, the use of appropriate in vivo and in vitro model systems appears to be vital in the generation of relevant experimental data. The intention of this review is to collate and discuss the currently available data on OTA-mediated toxicity with particular focus on their relevance for the in vivo situation, and also to suggest possible future strategies for unlocking the secrets of ochratoxin A.

SummaryThis study investigated the diversity of cyanobacterial mat communities of three meltwater ponds -Fresh, Orange and Salt Ponds, south of Bratina Island, McMurdo Ice Shelf, Antarctica. A combined morphological and genetic approach using clone libraries was used to investigate the influence of salinity on cyanobacterial diversity within these ecosystems without prior cultivation or isolation of cyanobacteria. We were able to identify 22 phylotypes belonging to Phormidium sp., Oscillatoria sp. and Lyngbya sp. In addition, we identified Antarctic Nostoc sp., Nodularia sp. and Anabaena sp. from the clone libraries. Fresh (17 phylotypes) and Orange (nine phylotypes) Ponds showed a similar diversity in contrast to that of the hypersaline Salt Pond (five phylotypes), where the diversity within cyanobacterial mats was reduced. Using the comparison of identified phylotypes with existing Antarctic sequence data, it was possible to gain further insight into the different levels of distribution of phylotypes identified in the investigated cyanobacterial mat communities of McMurdo Ice Shelf.

The presence of apoptotic cell death was determined using in situ fragment end labeling (ISEL) of the respective tissue sections and agarose gel electrophoresis for detection of DNA-laddering. The analysis of carp tissue extracts (hepatopancreas, kidney, GI tract, skeletal muscle, brain, heart, spleen, and gills) demonstrated MC-LR adducts having molecular weights of 38 kDa (putatively catalytic subunit of protein phosphatases-1 and -2A) and 28 kDa, respectively. An additional band was found to be present at 23 kDa in both hepatopancreas and kidney. The present data demonstrate that, in comparison to the pathological events in salmonids exposed to MC, where a slower development of pathology and primarily necrotic cell death prevails, the pathology in carp develops rapidly and at lower toxin concentrations. This is most likely due to a more efficient uptake of toxin, while the mechanism of cell death is primarily apoptosis.

Cyanobaeteria (blue-green algae) produee toxins that may present a hazard 101' drinking water safety, These toxins (mieroeystins, nodularins, saxitoxins, anatoxin-a, anatoxin-a(s), eylindrospermopsinl are strueturally diverse and their effeets range from liver damage, including liver cancer, to neurotoxicity, The oecurrenee of eyanobaetsria and their toxins in WeHer bodies used for tlle procluction 01 drinking water poses a tsehnieal cllallenge lor water utility managers, With respeet to their removal in water treatment procedures, of the more than 60 microcystln congeners, microeystin-LR (L, L-Ieucine; R, L-arglnine) is the best studied cyanobacterial toxin, whereas information for the other toxins is largely lacking, In response to the growing conCern about nanlethal aeute anel chronie eHeets 01 rnicrocystins, lhe World Health Organization has recently set a new provisional guideline value 101' microeystin-LR 011,0 IJg/L drinking water, This will lead to fwther sHorts by water suppliers to develap effective treatment procedures to remove these toxins, 01 the water treatment procedures discussed in this review, chlorination, possibly mierolultrafiltration, but especially 07.Onation are the most effective in destroying eyanobaeteria and in removing microcystins, However, these treatments may not be suflieient during bloom situations 01' when a high organie load is present, and toxin levels should therefore be monitorecl during lIle water treatment proeess, In order to perform an adeqllate human risk assessrnent of' mierocystin exposure via cJrinkinQ water, the issue of water treatment byproducts will have to be addressed in t!leluture. Kev words: cyanobacteria, ozone, risk assessment, toxin, water treatment. -Environ HealtlJ Perspect 108(sllppl 1):1' 13-122 (2000). IJttp://elJpne tl, nielJs, nilJ,gov/docs/2000/suppl-1/113-122hitzfeld/abstract,html