Genotoxic effects of Alternaria mycotoxins in human liver HepG2 cells

Ventura, Célia; Vilela, Rita Sofia; Guerreiro, Beatriz; Louro, Henriqueta; Silva, Maria João

http://hdl.handle.net/10400.18/11291

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Objective: Mycotoxins are natural toxic compounds produced by filamentous fungi as secondary metabolites. Human exposure to mycotoxins occurs predominantly through ingestion of contaminated food, and have been associated with nephrotoxicity, hepatotoxicity, immunotoxicity, carcinogenicity, and teratogenicity. Alternaria mycotoxins are produced by black moulds of the genus Alternaria, which are common plant pathogens and saprophytes widely distributed in the environment. However, limited toxicological data exists on Alternaria mycotoxins. Within the scope of the European Partnership for the Assessment of Risks from Chemicals (PARC; https://www.eu-parc.eu/) these toxins were considered as priority substances, and several studies are underway with the aim of filling knowledge gaps regarding their genotoxicity, among other toxic effects. Methods: Genotoxicity was evaluated using the In Vitro Mammalian Cell Micronucleus Assay with cytokinesis block (CBMN) according to the OECD TG 487. HepG2 liver cells were exposed for 48 h to a concentration-range of each Alternaria mycotoxin following dose-range finding based on cytotoxicity testing (MTT assay). Vinblastine was used as a positive control. Results: All tested mycotoxins were cytotoxic in the MTT assay and genotoxic in the CBMN assay. In addition to the significant increase in micronucleated binucleated cells, some mycotoxins also induced a significant increase in other nuclear anomalies in HepG2 cells, showing a dose-response relationship. Conclusions: These results indicate that the studied Alternaria mycotoxins induce chromosomal damage, which can lead to genomic instability, a key driver in cancer. Therefore, this study contributes to PARC objectives, providing critical toxicological data for their hazard assessment following human oral exposure. The data will contribute to support their risk assessment and management by regulators and policy makers in order to protect human health from these emerging food contaminants.