Dynamic cytotoxic response to microcystins using microelectronic sensor arrays
| Autor: | Dorothy Yu Huang, Jasna Dmitrovic, Melissa Mock, Stephan Gabos, Bruno Hagenbuch, Siu Chan, David Kinniburgh |
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| Rok vydání: | 2009 |
| Předmět: |
Cyanobacteria
Microcystins Metabolite Cell Tetrazolium Salts CHO Cells Organic Anion Transporters Sodium-Independent medicine.disease_cause chemistry.chemical_compound Mice Solute Carrier Organic Anion Transporter Family Member 1B3 Cricetulus Cricetinae Toxicity Tests polycyclic compounds medicine Environmental Chemistry Bioassay Animals Humans Cytotoxicity biology Chemistry Toxin Cell Membrane Environmental engineering General Chemistry biology.organism_classification In vitro Thiazoles medicine.anatomical_structure Biochemistry Cell culture Microelectrodes |
| Zdroj: | Environmental sciencetechnology. 43(20) |
| ISSN: | 0013-936X |
| Popis: | Microcystins are bioactive metabolites produced by cyanobacteria in water. These cyclic heptapeptides have caused public health concern worldwide. By interfering with cellular phosphorylation and signaling, microcystins can cause acute and chronic liver diseases. Therefore, the World Health Organization (WHO) has set the provisional drinking water guideline value at 1.0 microg/L for microcystin-LR (free plus cell-bound). Microcystins do not readily cross cell membranes in in vitro cell-based assays, except for those using freshly isolated hepatocytes. However, the sensitivity of in vitro cell-based assays is not adequate for testing samples at low environmental concentrations. Hence, there is a need to develop a sensitive and stable cytotoxicity assay for use in environmental studies. On the basis of the observation that microcystin-LR can be transported by the liver-specific members of the organic anion transporting polypeptides (OATPs), we investigated the potential of using an OATP1B3-expressing cell line in a cytotoxicity assay for microcystins. Using a novel cell electronic sensing system (RT-CES), we were able to monitor the real-time, dynamic cytotoxic response to microcystins at microgram per liter concentrations. We demonstrated that the cytotoxicity of the most common microcystins, -LR, -YR, -RR, -LF, and -LW, was mediated by OATP1B3 transporters. Microcystin-LF is the most potent toxin among the five congeners. In conclusion, we have established a highly automated, real-time, sensitive, and stable assay for measuring microcystin cytoxicity. |
| Databáze: | OpenAIRE |
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