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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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