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@article{1419437,
author = {Raška, Jan and Čtveráčková, Lucie and Dydowiczová, Aneta and Sovadinová, Iva and Bláha, Luděk and Babica, Pavel},
article_location = {SAN DIEGO},
article_number = {April},
doi = {http://dx.doi.org/10.1016/j.taap.2018.03.011},
keywords = {HL1-hT1; Microcystin-LR; Adult liver stem cells; Liver tumor-promotion; OATP; Multidrug resistance proteins},
language = {eng},
issn = {0041-008X},
journal = {Toxicology and applied pharmacology},
title = {Tumor-promoting cyanotoxin microcystin-LR does not induce procarcinogenic events in adult human liver stem cells},
url = {https://www.sciencedirect.com/science/article/pii/S0041008X18300899?via%3Dihub},
volume = {345},
year = {2018}
}
TY - JOUR
ID - 1419437
AU - Raška, Jan - Čtveráčková, Lucie - Dydowiczová, Aneta - Sovadinová, Iva - Bláha, Luděk - Babica, Pavel
PY - 2018
TI - Tumor-promoting cyanotoxin microcystin-LR does not induce procarcinogenic events in adult human liver stem cells
JF - Toxicology and applied pharmacology
VL - 345
IS - April
SP - 103-113
EP - 103-113
PB - ACADEMIC PRESS INC ELSEVIER SCIENCE
SN - 0041008X
KW - HL1-hT1
KW - Microcystin-LR
KW - Adult liver stem cells
KW - Liver tumor-promotion
KW - OATP
KW - Multidrug resistance proteins
UR - https://www.sciencedirect.com/science/article/pii/S0041008X18300899?via%3Dihub
L2 - https://www.sciencedirect.com/science/article/pii/S0041008X18300899?via%3Dihub
N2 - HL1-hT1 cell line represents adult human liver stem cells (LSCs) immortalized with human telomerase reverse transcriptase. In this study, HL1-hT1 cells were found to express mesenchymal markers (vimentin, CD73, CD90/THY-1 and CD105) and an early hepatic endoderm marker FOXA2, while not expressing hepatic progenitor (HNF4A, LGR5, alpha-fetoprotein) or differentiated hepatocyte markers (albumin, transthyretin, connexin 32). In response to microcystin-LR (MC-LR), a time- and concentration-dependent formation of MC-positive protein bands in HL1-hT1 cells was observed. Cellular accumulation of MC-LR occurred most likely via mechanisms independent on organic anion transporting polypeptides (OATPs) or multidrug resistance (MDR) proteins, as indicated (a) by a gene expression analysis of 11 human OATP genes and 4 major MDR genes (MDR1/P-gly-coprotein, MRP1, MRP2 and BCRP); (b) by non-significant effects of OATP or MDR1 inhibitors on MC-LR uptake. Accumulation of MC-positive protein bands in HL1-hT1 cells was associated neither with alterations of cell viability and growth, dysregulations of ERK1/2 and p38 kinases, reactive oxygen species formation, induction of double-stranded DNA breaks nor modulations of stress-inducible genes (ATF3, HSP5). It suggests that LSCs might have a selective, MDR1-independent, survival advantage and higher tolerance towards MC-induced cytotoxic, genotoxic or cancer-related events than differentiated adult hepatocytes, fetal hepatocyte or malignant liver cell lines. HL1-hT1 cells provide a valuable in vitro tool for studying effects of toxicants and pharmaceuticals on LSCs, whose important role in the development of chronic toxicities and liver diseases is being increasingly recognized.
ER -
RAŠKA, Jan, Lucie ČTVERÁČKOVÁ, Aneta DYDOWICZOVÁ, Iva SOVADINOVÁ, Luděk BLÁHA and Pavel BABICA. Tumor-promoting cyanotoxin microcystin-LR does not induce procarcinogenic events in adult human liver stem cells. \textit{Toxicology and applied pharmacology}. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE, 2018, vol.~345, April, p.~103-113. ISSN~0041-008X. Available from: https://dx.doi.org/10.1016/j.taap.2018.03.011.
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