Impact of Deoxynivalenol and Zearalenone as Single and Combined Treatment on DNA, Cell Cycle and Cell Proliferation in HepG2 Cells

Domijan, Ana-Marija; Hercog, Klara; Štampar, Martina; Gajski, Goran; Gerić, Marko; Sokolović, Marijana; Žegura, Bojana

doi:10.3390/ijms24044082

Open AccessArticle

Impact of Deoxynivalenol and Zearalenone as Single and Combined Treatment on DNA, Cell Cycle and Cell Proliferation in HepG2 Cells

by

Ana-Marija Domijan

^1,*,

Klara Hercog

²,

Martina Štampar

²

,

Goran Gajski

³

,

Marko Gerić

³,

Marijana Sokolović

⁴

and

Bojana Žegura

²

¹

Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia

²

Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia

³

Mutagenesis Unit, Institute for Medical Research and Occupational Health, 10000 Zagreb, Croatia

⁴

Poultry Center, Croatian Veterinary Institute, 10000 Zagreb, Croatia

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2023, 24(4), 4082; https://doi.org/10.3390/ijms24044082

Submission received: 30 January 2023 / Revised: 13 February 2023 / Accepted: 15 February 2023 / Published: 17 February 2023

(This article belongs to the Special Issue Future Perspectives of Cell-Based Research in Toxicology and Drug Discovery)

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Abstract

The study aimed to investigate toxicity and the mechanism of toxicity of two Fusarium mycotoxins, deoxynivalenol (DON) and zearalenone (ZEA). DON and ZEA were applied to HepG2 cells as single compounds and in combination at low environmentally relevant concentrations. HepG2 cells were exposed to DON (0.5, 1, and 2 µM), ZEA (5, 10, and 20 µM) or their combinations (1 µM DON + 5 µM ZEA, 1 µM DON + 10 µM ZEA and 1 µM DON + 20 µM ZEA) for 24 h and cell viability, DNA damage, cell cycle and proliferation were assessed. Both mycotoxins reduced cell viability, however, combined treatment with DON and ZEA resulted in higher reduction of cell viability. DON (1 µM) induced primary DNA damage, while DON (1 µM) in combination with higher ZEA concentrations showed antagonistic effects compared to DON alone at 1 µM. DON arrested HepG2 cells in G2 phase and significantly inhibited cell proliferation, while ZEA had no significant effect on cell cycle. The combined treatment with DON and ZEA arrested cells in G2 phase to a higher extend compared to treatment with single mycotoxins. Potentiating effect observed after DON and ZEA co-exposure at environmentally relevant concentrations indicates that in risk assessment and setting governments’ regulations, mixtures of mycotoxins should be considered.

Keywords: mycotoxins; comet assay; flow cytometry; co-exposure; food monitoring

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MDPI and ACS Style

Domijan, A.-M.; Hercog, K.; Štampar, M.; Gajski, G.; Gerić, M.; Sokolović, M.; Žegura, B. Impact of Deoxynivalenol and Zearalenone as Single and Combined Treatment on DNA, Cell Cycle and Cell Proliferation in HepG2 Cells. Int. J. Mol. Sci. 2023, 24, 4082. https://doi.org/10.3390/ijms24044082

AMA Style

Domijan A-M, Hercog K, Štampar M, Gajski G, Gerić M, Sokolović M, Žegura B. Impact of Deoxynivalenol and Zearalenone as Single and Combined Treatment on DNA, Cell Cycle and Cell Proliferation in HepG2 Cells. International Journal of Molecular Sciences. 2023; 24(4):4082. https://doi.org/10.3390/ijms24044082

Chicago/Turabian Style

Domijan, Ana-Marija, Klara Hercog, Martina Štampar, Goran Gajski, Marko Gerić, Marijana Sokolović, and Bojana Žegura. 2023. "Impact of Deoxynivalenol and Zearalenone as Single and Combined Treatment on DNA, Cell Cycle and Cell Proliferation in HepG2 Cells" International Journal of Molecular Sciences 24, no. 4: 4082. https://doi.org/10.3390/ijms24044082

APA Style

Domijan, A.-M., Hercog, K., Štampar, M., Gajski, G., Gerić, M., Sokolović, M., & Žegura, B. (2023). Impact of Deoxynivalenol and Zearalenone as Single and Combined Treatment on DNA, Cell Cycle and Cell Proliferation in HepG2 Cells. International Journal of Molecular Sciences, 24(4), 4082. https://doi.org/10.3390/ijms24044082

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Impact of Deoxynivalenol and Zearalenone as Single and Combined Treatment on DNA, Cell Cycle and Cell Proliferation in HepG2 Cells

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