Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line

Simultaneous occurrence of cylindrospermopsin (CYN) and microcystin-LR (MCLR) has been reported in the aquatic environment and thus human exposure to such mixtures is possible. As data on the combined effects of CYN/MCLR are scarce, we aimed to investigate the adverse effects related to genotoxic ac...

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Autores: Díez-Quijada Jiménez, Leticia, Hercog, Klara, Štampar, Martina, Filipič, Metka, Cameán Fernández, Ana María, Jos Gallego, Ángeles Mencía, Žegura, Bojana
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/127694
Acceso en línea:https://hdl.handle.net/11441/127694
https://doi.org/10.3390/toxins12120778
Access Level:acceso abierto
Palabra clave:DNA double-strand breaks
cell-cycle
mRNA expression
microcystin-LR
cylindrospermopsin
mixture
HepG2 cells
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spelling Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell LineDíez-Quijada Jiménez, LeticiaHercog, KlaraŠtampar, MartinaFilipič, MetkaCameán Fernández, Ana MaríaJos Gallego, Ángeles MencíaŽegura, BojanaDNA double-strand breakscell-cyclemRNA expressionmicrocystin-LRcylindrospermopsinmixtureHepG2 cellsSimultaneous occurrence of cylindrospermopsin (CYN) and microcystin-LR (MCLR) has been reported in the aquatic environment and thus human exposure to such mixtures is possible. As data on the combined effects of CYN/MCLR are scarce, we aimed to investigate the adverse effects related to genotoxic activities induced by CYN (0.125, 0.25 and 0.5 µg/mL) and MCLR (1 µg/mL) as single compounds and their combinations in HepG2 cells after 24 and 72 h exposure. CYN and CYN/MCLR induced DNA double-strand breaks after 72 h exposure, while cell cycle analysis revealed that CYN and CYN/MCLR arrested HepG2 cells in G0/G1 phase. Moreover, CYN and the combination with MCLR upregulated CYP1A1 and target genes involved in DNA-damage response (CDKN1A, GADD45A). Altogether, the results showed that after 72 h exposure genotoxic activity of CYN/MCLR mixture was comparable to the one of pure CYN. On the contrary, MCLR (1 µg/mL) had no effect on the viability of cells and had no influence on cell division. It did not induce DNA damage and did not deregulate studied genes after prolonged exposure. The outcomes of the study confirm the importance of investigating the combined effects of several toxins as the effects can differ from those induced by single compounds.Ministerio de Economía y Competitividad AGL2015-64558-RMinisterio de Ciencia, Innovación y Universidades PID2019-104890RB-I00European Cooperation in Science and Technology COST Action ES1105MDPINutrición y Bromatología, Toxicología y Medicina LegalMinisterio de Economía y Competitividad (MINECO). EspañaMinisterio de Ciencia, Innovación y Universidades (MICINN). EspañaEuropean Cooperation in Science and Technology (COST)2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/127694https://doi.org/10.3390/toxins12120778reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésToxins, 12 (12), 778.AGL2015-64558-RPID2019-104890RB-I00ES1105https://doi.org/10.3390/toxins12120778info:eu-repo/semantics/openAccessoai:idus.us.es:11441/1276942026-06-17T12:51:07Z
dc.title.none.fl_str_mv Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line
title Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line
spellingShingle Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line
Díez-Quijada Jiménez, Leticia
DNA double-strand breaks
cell-cycle
mRNA expression
microcystin-LR
cylindrospermopsin
mixture
HepG2 cells
title_short Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line
title_full Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line
title_fullStr Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line
title_full_unstemmed Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line
title_sort Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line
dc.creator.none.fl_str_mv Díez-Quijada Jiménez, Leticia
Hercog, Klara
Štampar, Martina
Filipič, Metka
Cameán Fernández, Ana María
Jos Gallego, Ángeles Mencía
Žegura, Bojana
author Díez-Quijada Jiménez, Leticia
author_facet Díez-Quijada Jiménez, Leticia
Hercog, Klara
Štampar, Martina
Filipič, Metka
Cameán Fernández, Ana María
Jos Gallego, Ángeles Mencía
Žegura, Bojana
author_role author
author2 Hercog, Klara
Štampar, Martina
Filipič, Metka
Cameán Fernández, Ana María
Jos Gallego, Ángeles Mencía
Žegura, Bojana
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Nutrición y Bromatología, Toxicología y Medicina Legal
Ministerio de Economía y Competitividad (MINECO). España
Ministerio de Ciencia, Innovación y Universidades (MICINN). España
European Cooperation in Science and Technology (COST)
dc.subject.none.fl_str_mv DNA double-strand breaks
cell-cycle
mRNA expression
microcystin-LR
cylindrospermopsin
mixture
HepG2 cells
topic DNA double-strand breaks
cell-cycle
mRNA expression
microcystin-LR
cylindrospermopsin
mixture
HepG2 cells
description Simultaneous occurrence of cylindrospermopsin (CYN) and microcystin-LR (MCLR) has been reported in the aquatic environment and thus human exposure to such mixtures is possible. As data on the combined effects of CYN/MCLR are scarce, we aimed to investigate the adverse effects related to genotoxic activities induced by CYN (0.125, 0.25 and 0.5 µg/mL) and MCLR (1 µg/mL) as single compounds and their combinations in HepG2 cells after 24 and 72 h exposure. CYN and CYN/MCLR induced DNA double-strand breaks after 72 h exposure, while cell cycle analysis revealed that CYN and CYN/MCLR arrested HepG2 cells in G0/G1 phase. Moreover, CYN and the combination with MCLR upregulated CYP1A1 and target genes involved in DNA-damage response (CDKN1A, GADD45A). Altogether, the results showed that after 72 h exposure genotoxic activity of CYN/MCLR mixture was comparable to the one of pure CYN. On the contrary, MCLR (1 µg/mL) had no effect on the viability of cells and had no influence on cell division. It did not induce DNA damage and did not deregulate studied genes after prolonged exposure. The outcomes of the study confirm the importance of investigating the combined effects of several toxins as the effects can differ from those induced by single compounds.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/11441/127694
https://doi.org/10.3390/toxins12120778
url https://hdl.handle.net/11441/127694
https://doi.org/10.3390/toxins12120778
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Toxins, 12 (12), 778.
AGL2015-64558-R
PID2019-104890RB-I00
ES1105
https://doi.org/10.3390/toxins12120778
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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