Genotoxic effects of the ochratoxin A (OTA), its main metabolite (OTα) per se and in combination with fumonisin B1 in HepG2 cells and human lymphocytes

Abstract

Ochratoxin A (OTA) and fumonisin B1 (FB1) are mycotoxins distributed in a wide variety of foods for human or animal consumption and are classified as possible carcinogens for humans. This study aimed to evaluate the cytotoxic, cytostatic and genotoxic effects of OTA and its main metabolite, ochratoxin α (OTα), FB1 and three combinations of OTA and FB1 at moderate and environmental doses. Cell viability was evaluated through MTT assay and the trypan blue exclusion method. The cytostatic and genotoxic effects were evaluated through the cytokinesis-block micronucleus assay. The results showed synergistic time- and concentration-dependent cytotoxic effects of one of the combinations of OTA and FB1. In contrast, significant differences were observed in the micronuclei (MN) frequency from OTA, OTα and coexposure of OTA + FB1. Some of these combinations increased the frequency of nuclear buds, nucleoplasmic bridges, donut-shaped nuclei, necrotic and apoptotic cells and MN in mononucleated cells. In conclusion, OTA and its main metabolite OTα, as well as the co-exposure of OTA and FB1, cause stable DNA damage at environmentally relevant concentrations, which was greater in metabolically competent cells. More studies are needed to understand the chemical interactions that occur due to the joint presence of mycotoxins, which occurs commonly.