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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Autor*in:	Leticia Díez-Quijada [verfasserIn] Klara Hercog [verfasserIn] Martina Štampar [verfasserIn] Metka Filipič [verfasserIn] Ana M. Cameán [verfasserIn] Ángeles Jos [verfasserIn] Bojana Žegura [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	DNA double-strand breaks cell-cycle mRNA expression microcystin-LR cylindrospermopsin mixture

Übergeordnetes Werk:	In: Toxins - MDPI AG, 2010, 12(2020), 12, p 778
Übergeordnetes Werk:	volume:12 ; year:2020 ; number:12, p 778

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/toxins12120778

Katalog-ID:	DOAJ085485438

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520			\|a 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 <i<CYP1A1</i< and target genes involved in DNA-damage response (<i<CDKN1A</i<, <i<GADD45A</i<). 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.
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allfields	10.3390/toxins12120778 doi (DE-627)DOAJ085485438 (DE-599)DOAJ720b863a39e842e1b7f3bd3df1fc8adc DE-627 ger DE-627 rakwb eng Leticia Díez-Quijada verfasserin aut Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 <i<CYP1A1</i< and target genes involved in DNA-damage response (<i<CDKN1A</i<, <i<GADD45A</i<). 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. DNA double-strand breaks cell-cycle mRNA expression microcystin-LR cylindrospermopsin mixture Medicine R Klara Hercog verfasserin aut Martina Štampar verfasserin aut Metka Filipič verfasserin aut Ana M. Cameán verfasserin aut Ángeles Jos verfasserin aut Bojana Žegura verfasserin aut In Toxins MDPI AG, 2010 12(2020), 12, p 778 (DE-627)610604236 (DE-600)2518395-3 20726651 nnns volume:12 year:2020 number:12, p 778 https://doi.org/10.3390/toxins12120778 kostenfrei https://doaj.org/article/720b863a39e842e1b7f3bd3df1fc8adc kostenfrei https://www.mdpi.com/2072-6651/12/12/778 kostenfrei https://doaj.org/toc/2072-6651 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 12, p 778
spelling	10.3390/toxins12120778 doi (DE-627)DOAJ085485438 (DE-599)DOAJ720b863a39e842e1b7f3bd3df1fc8adc DE-627 ger DE-627 rakwb eng Leticia Díez-Quijada verfasserin aut Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 <i<CYP1A1</i< and target genes involved in DNA-damage response (<i<CDKN1A</i<, <i<GADD45A</i<). 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. DNA double-strand breaks cell-cycle mRNA expression microcystin-LR cylindrospermopsin mixture Medicine R Klara Hercog verfasserin aut Martina Štampar verfasserin aut Metka Filipič verfasserin aut Ana M. Cameán verfasserin aut Ángeles Jos verfasserin aut Bojana Žegura verfasserin aut In Toxins MDPI AG, 2010 12(2020), 12, p 778 (DE-627)610604236 (DE-600)2518395-3 20726651 nnns volume:12 year:2020 number:12, p 778 https://doi.org/10.3390/toxins12120778 kostenfrei https://doaj.org/article/720b863a39e842e1b7f3bd3df1fc8adc kostenfrei https://www.mdpi.com/2072-6651/12/12/778 kostenfrei https://doaj.org/toc/2072-6651 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 12, p 778
allfields_unstemmed	10.3390/toxins12120778 doi (DE-627)DOAJ085485438 (DE-599)DOAJ720b863a39e842e1b7f3bd3df1fc8adc DE-627 ger DE-627 rakwb eng Leticia Díez-Quijada verfasserin aut Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 <i<CYP1A1</i< and target genes involved in DNA-damage response (<i<CDKN1A</i<, <i<GADD45A</i<). 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. DNA double-strand breaks cell-cycle mRNA expression microcystin-LR cylindrospermopsin mixture Medicine R Klara Hercog verfasserin aut Martina Štampar verfasserin aut Metka Filipič verfasserin aut Ana M. Cameán verfasserin aut Ángeles Jos verfasserin aut Bojana Žegura verfasserin aut In Toxins MDPI AG, 2010 12(2020), 12, p 778 (DE-627)610604236 (DE-600)2518395-3 20726651 nnns volume:12 year:2020 number:12, p 778 https://doi.org/10.3390/toxins12120778 kostenfrei https://doaj.org/article/720b863a39e842e1b7f3bd3df1fc8adc kostenfrei https://www.mdpi.com/2072-6651/12/12/778 kostenfrei https://doaj.org/toc/2072-6651 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 12, p 778
allfieldsGer	10.3390/toxins12120778 doi (DE-627)DOAJ085485438 (DE-599)DOAJ720b863a39e842e1b7f3bd3df1fc8adc DE-627 ger DE-627 rakwb eng Leticia Díez-Quijada verfasserin aut Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 <i<CYP1A1</i< and target genes involved in DNA-damage response (<i<CDKN1A</i<, <i<GADD45A</i<). 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. DNA double-strand breaks cell-cycle mRNA expression microcystin-LR cylindrospermopsin mixture Medicine R Klara Hercog verfasserin aut Martina Štampar verfasserin aut Metka Filipič verfasserin aut Ana M. Cameán verfasserin aut Ángeles Jos verfasserin aut Bojana Žegura verfasserin aut In Toxins MDPI AG, 2010 12(2020), 12, p 778 (DE-627)610604236 (DE-600)2518395-3 20726651 nnns volume:12 year:2020 number:12, p 778 https://doi.org/10.3390/toxins12120778 kostenfrei https://doaj.org/article/720b863a39e842e1b7f3bd3df1fc8adc kostenfrei https://www.mdpi.com/2072-6651/12/12/778 kostenfrei https://doaj.org/toc/2072-6651 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 12, p 778
allfieldsSound	10.3390/toxins12120778 doi (DE-627)DOAJ085485438 (DE-599)DOAJ720b863a39e842e1b7f3bd3df1fc8adc DE-627 ger DE-627 rakwb eng Leticia Díez-Quijada verfasserin aut Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 <i<CYP1A1</i< and target genes involved in DNA-damage response (<i<CDKN1A</i<, <i<GADD45A</i<). 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. DNA double-strand breaks cell-cycle mRNA expression microcystin-LR cylindrospermopsin mixture Medicine R Klara Hercog verfasserin aut Martina Štampar verfasserin aut Metka Filipič verfasserin aut Ana M. Cameán verfasserin aut Ángeles Jos verfasserin aut Bojana Žegura verfasserin aut In Toxins MDPI AG, 2010 12(2020), 12, p 778 (DE-627)610604236 (DE-600)2518395-3 20726651 nnns volume:12 year:2020 number:12, p 778 https://doi.org/10.3390/toxins12120778 kostenfrei https://doaj.org/article/720b863a39e842e1b7f3bd3df1fc8adc kostenfrei https://www.mdpi.com/2072-6651/12/12/778 kostenfrei https://doaj.org/toc/2072-6651 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2020 12, p 778
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author	Leticia Díez-Quijada
spellingShingle	Leticia Díez-Quijada misc DNA double-strand breaks misc cell-cycle misc mRNA expression misc microcystin-LR misc cylindrospermopsin misc mixture misc Medicine misc R Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line
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topic_title	Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line DNA double-strand breaks cell-cycle mRNA expression microcystin-LR cylindrospermopsin mixture
topic	misc DNA double-strand breaks misc cell-cycle misc mRNA expression misc microcystin-LR misc cylindrospermopsin misc mixture misc Medicine misc R
topic_unstemmed	misc DNA double-strand breaks misc cell-cycle misc mRNA expression misc microcystin-LR misc cylindrospermopsin misc mixture misc Medicine misc R
topic_browse	misc DNA double-strand breaks misc cell-cycle misc mRNA expression misc microcystin-LR misc cylindrospermopsin misc mixture misc Medicine misc R
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title	Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line
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title_full	Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line
author_sort	Leticia Díez-Quijada
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author_browse	Leticia Díez-Quijada Klara Hercog Martina Štampar Metka Filipič Ana M. Cameán Ángeles Jos Bojana Žegura
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title_sort	genotoxic effects of cylindrospermopsin, microcystin-lr and their binary mixture in human hepatocellular carcinoma (hepg2) cell line
title_auth	Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line
abstract	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 <i<CYP1A1</i< and target genes involved in DNA-damage response (<i<CDKN1A</i<, <i<GADD45A</i<). 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.
abstractGer	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 <i<CYP1A1</i< and target genes involved in DNA-damage response (<i<CDKN1A</i<, <i<GADD45A</i<). 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.
abstract_unstemmed	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 <i<CYP1A1</i< and target genes involved in DNA-damage response (<i<CDKN1A</i<, <i<GADD45A</i<). 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.
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title_short	Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line
url	https://doi.org/10.3390/toxins12120778 https://doaj.org/article/720b863a39e842e1b7f3bd3df1fc8adc https://www.mdpi.com/2072-6651/12/12/778 https://doaj.org/toc/2072-6651
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author2	Klara Hercog Martina Štampar Metka Filipič Ana M. Cameán Ángeles Jos Bojana Žegura
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doi_str	10.3390/toxins12120778
up_date	2024-07-03T15:01:32.481Z
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Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line

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