The secondary Fusarium metabolite aurofusarin induces oxidative stress, cytotoxicity and genotoxicity in human colon cells. (1st March 2018)

• Record Type: Journal Article
• Authors: Jarolim, Katharina; Wolters, Konstantin; Woelflingseder, Lydia; Pahlke, Gudrun; Beisl, Julia; Puntscher, Hannes; Braun, Dominik; Sulyok, Michael; Warth, Benedikt; Marko, Doris
• Is Part Of: Toxicology letters. Volume 284(2018)
• Page Start: 170
• Page End: 183
• Publication Date: 2018-03-01
• Subjects: Mycotoxin -- Aurofusarin -- Food safety -- Cytotoxicity -- Genotoxicity -- Reactive oxygen species; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2017.12.008
• Languages: English
• ISSNs: 0378-4274

Abstract

Graphical abstract: Highlights: Aurofusarin (AURO) mediates cytotoxic effects in HT29 and HCEC-1CT cells. AURO induces enhanced levels of p53 but not γH2AX. Induction of DNA damage in the comet assay including fpg sensitive sites. AURO mediates oxidative stress but no Nrf2 activation. AURO acts as an inducer of CYP1A1. Abstract: Aurofusarin (AURO), a dimeric naphthoquinone, is produced by Fusarium fungi. Although frequently found in food and feed, toxicological studies are limited. Hence, the in vitro toxicity of AURO was investigated in the colon adenocarcinoma cell line HT29 and the non-tumorigenic colon cells HCEC-1CT. Cytotoxic effects were found at concentrations ≥1 μM by evaluating mitochondrial activity (WST-1) and cellular proliferation (sulforhodamine B assay). 10 μM of AURO induced a decrease of cells in the S-phase, measured by flow cytometry. Confocal microscopy revealed AURO-mediated increase of intracellular p53 protein. In accordance, DNA-damage was seen in the comet assay (≥1 μM) together with enhanced levels of formamidopyrimidine-DNA-glycosylase (fpg)-sensitive sites, indicative for oxidative stress. An increase of intracellular reactive oxygen species was observed in the dichlorofluorescein (DCF) assay (≥5 μM). The GSSG/GSH ratio was elevated, but no impact on redox-sensitive Nrf2-dependent genes (Nrf2, γ-GCL, NQO1) was found at the gene expression level. However, induction of cytochrome P450 monooxygenase (CYP) 1A1 was measured at the gene expression and protein level. In conclusion, these in vitro data suggest that, when co-occurring, AURO might be considered as a potential contributor to the overall toxicity of respective Fusarium mycotoxin mixtures.