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Article

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

1
Area of Toxicology, Faculty of Pharmacy, Universidad de Sevilla, Profesor García González No. 2, 41012 Seville, Spain
2
Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, 1000 Ljubljana, Slovenia
3
Jozef Stefan International Postgraduate School, Jamova 39, 1000 Ljubljana, Slovenia
*
Author to whom correspondence should be addressed.
Received: 13 October 2020 / Revised: 26 November 2020 / Accepted: 5 December 2020 / Published: 8 December 2020
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. View Full-Text
Keywords: DNA double-strand breaks; cell-cycle; mRNA expression; microcystin-LR; cylindrospermopsin; mixture; HepG2 cells DNA double-strand breaks; cell-cycle; mRNA expression; microcystin-LR; cylindrospermopsin; mixture; HepG2 cells
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MDPI and ACS Style

Díez-Quijada, L.; Hercog, K.; Štampar, M.; Filipič, M.; Cameán, A.M.; Jos, Á.; Žegura, B. Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line. Toxins 2020, 12, 778. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12120778

AMA Style

Díez-Quijada L, Hercog K, Štampar M, Filipič M, Cameán AM, Jos Á, Žegura B. Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line. Toxins. 2020; 12(12):778. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12120778

Chicago/Turabian Style

Díez-Quijada, Leticia, Klara Hercog, Martina Štampar, Metka Filipič, Ana M. Cameán, Ángeles Jos, and Bojana Žegura. 2020. "Genotoxic Effects of Cylindrospermopsin, Microcystin-LR and Their Binary Mixture in Human Hepatocellular Carcinoma (HepG2) Cell Line" Toxins 12, no. 12: 778. https://0-doi-org.brum.beds.ac.uk/10.3390/toxins12120778

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