Combined cytotoxic and genotoxic effects of ochratoxin A and fumonisin B in human kidney and liver cell models.

M Pinhão, A M Tavares, S Loureiro, H Louro, P Alvito, M J Silva

Journal: Toxicology in vitro : an international journal published in association with BIBRA 2021;68():104949

PMID: 32717212

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Abstract

Food products can be contaminated by several fungi species and each species may produce different mycotoxins, leading to human combined exposure. Although predictions about the joint toxic effects of mycotoxins can be made from their individual toxicities, experimental data is still limited to allow a reliable hazard assessment. Thus, this study aimed to characterize the combined cytotoxic and genotoxic effects of ochratoxin A (OTA) and fumonisin B1 (FB) in cell lines representative of their target organs, kidney and liver. Interactions were ascertained using mathematical extensions to the reference models of concentration addition and independent action. Cytotoxicity (MTT assay) data modeling revealed a synergistic pattern for low doses of both FB and OTA shifting to antagonism at higher concentration levels, irrespectively of the reference model applied. Concerning genotoxicity assessment, neither OTA nor FB, individually or in combination, induced a prominent increase in DNA damage (comet assay) or oxidative DNA damage (FPG-comet assay). In conclusion, this study revealed a synergistic cytotoxic effect for OTA and FB at low concentration levels. Given that human co-exposure to these two mycotoxins is probable to occur at low doses, these results raise concerns regarding their potential health outcomes that seem to differ from those predicted by an additive model.

Address: Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, I.P. (INSA), Av. Padre Cruz, 1649-016 Lisbon, Portugal. Electronic address: [email protected].; Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, I.P. (INSA), Av. Padre Cruz, 1649-016 Lisbon, Portugal. Electronic address: [email protected].; CESAM - Centre for Environmental and Marine Studies, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal. Electronic address: [email protected].; Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, I.P. (INSA), Av. Padre Cruz, 1649-016 Lisbon, Portugal; ToxOmics - Centre for Toxicogenomics and Human Health, NOVA Medical School/FCM, Universidade NOVA de Lisboa, Portugal. Electronic address: [email protected].; CESAM - Centre for Environmental and Marine Studies, Universidade de Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal; Food and Nutrition Department, INSA, Av. Padre Cruz, 1649-016 Lisboa, Portugal. Electronic address: [email protected].; Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, I.P. (INSA), Av. Padre Cruz, 1649-016 Lisbon, Portugal; ToxOmics - Centre for Toxicogenomics and Human Health, NOVA Medical School/FCM, Universidade NOVA de Lisboa, Portugal. Electronic address: [email protected].

DOI: 10.1016/j.tiv.2020.104949

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MeSH Terms: Cell Line, DNA Damage, Drug Synergism, Fumonisins, Humans, Kidney, Liver, Mutagens, Ochratoxins, Oxidative Stress