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@article{1488086, author = {Basu, Amrita and Dydowiczová, Aneta and Čtveráčková, Lucie and Jaša, Libor and Trosko, James E. and Bláha, Luděk and Babica, Pavel}, article_location = {WASHINGTON}, article_number = {17}, doi = {http://dx.doi.org/10.1021/acs.est.8b02291}, keywords = {PRIMARY RAT HEPATOCYTES; HUMAN HEPATOMA-CELLS; MICROCYSTIN-LR; ALKALOID CYLINDROSPERMOPSIN; 1ST IDENTIFICATION; OXIDATIVE STRESS; SOUTHWEST CHINA; GENE-EXPRESSION; HL7702 CELLS; CYTOTOXICITY}, language = {eng}, issn = {0013-936X}, journal = {ENVIRONMENTAL SCIENCE & TECHNOLOGY}, title = {Assessment of Hepatotoxic Potential of Cyanobacterial Toxins Using 3D In Vitro Model of Adult Human Liver Stem Cells}, url = {https://pubs.acs.org/doi/10.1021/acs.est.8b02291}, volume = {52}, year = {2018} }
TY - JOUR ID - 1488086 AU - Basu, Amrita - Dydowiczová, Aneta - Čtveráčková, Lucie - Jaša, Libor - Trosko, James E. - Bláha, Luděk - Babica, Pavel PY - 2018 TI - Assessment of Hepatotoxic Potential of Cyanobacterial Toxins Using 3D In Vitro Model of Adult Human Liver Stem Cells JF - ENVIRONMENTAL SCIENCE & TECHNOLOGY VL - 52 IS - 17 SP - 10078-10088 EP - 10078-10088 PB - AMER CHEMICAL SOC SN - 0013936X KW - PRIMARY RAT HEPATOCYTES KW - HUMAN HEPATOMA-CELLS KW - MICROCYSTIN-LR KW - ALKALOID CYLINDROSPERMOPSIN KW - 1ST IDENTIFICATION KW - OXIDATIVE STRESS KW - SOUTHWEST CHINA KW - GENE-EXPRESSION KW - HL7702 CELLS KW - CYTOTOXICITY UR - https://pubs.acs.org/doi/10.1021/acs.est.8b02291 L2 - https://pubs.acs.org/doi/10.1021/acs.est.8b02291 N2 - Cyanotoxins microcystin-LR (MC-LR) and cylindrospermopsin (CYN) represent hazardous waterborne contaminants and potent human hepatotoxins. However, in vitro monolayer cultures of hepatic cell lines were found to recapitulate, poorly, major hepatocyte-specific functions and inadequately predict hepatotoxic effects of MC-LR and CYN. We utilized 3-dimensional (3D), scaffold-free spheroid cultures of human telomerase-immortalized adult liver stem cells HL1-hT1 to evaluate hepatotoxic potential of MC-LR and CYN. In monolayer cultures of HL1-hT1 cells, MC-LR did not induce cytotoxic effects (EC50 > 10 micromol/L), while CYN inhibited cell growth and viability (48h-96h EC50 approximate to 5.5-0.6 micromol/L). Growth and viability of small growing spheroids were inhibited by both cyanotoxins (>= 0.1 micromol/L) and were associated with blebbing and disintegration at the spheroid surface. Hepatospheroid damage and viability reduction were observed also in large mature spheroids, with viability 96h-EC50 values being 0.04 micromol/L for MC-LR and 0.1 micromol/L for CYN, and No Observed Effect Concentrations <0.01 micromol/L. Spheroid cultures of adult human liver stem cells HL1-hT1 exhibit sensitivity comparable to cultures of primary hepatocytes and provide a simple, practical, and cost-effective tool, which can be effectively used in environmental and toxicological research, including assessment of hepatotoxic potential and effect-based monitoring of various samples contaminated with toxic cyanobacteria. ER -
BASU, Amrita, Aneta DYDOWICZOVÁ, Lucie ČTVERÁČKOVÁ, Libor JAŠA, James E. TROSKO, Luděk BLÁHA a Pavel BABICA. Assessment of Hepatotoxic Potential of Cyanobacterial Toxins Using 3D In Vitro Model of Adult Human Liver Stem Cells. \textit{ENVIRONMENTAL SCIENCE \&{}amp; TECHNOLOGY}. WASHINGTON: AMER CHEMICAL SOC, 2018, roč.~52, č.~17, s.~10078-10088. ISSN~0013-936X. Dostupné z: https://dx.doi.org/10.1021/acs.est.8b02291.
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