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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 and 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, vol.~52, No~17, p.~10078-10088. ISSN~0013-936X. Available from: https://dx.doi.org/10.1021/acs.est.8b02291.
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