Abstract
Alternaria molds simultaneously produce a large variety of mycotoxins, of which several were previously reported to induce enzymes of phase I metabolism through aryl hydrocarbon receptor activation. Thus, we investigated the potential of naturally occurring Alternaria toxin mixtures to induce Cytochrome P450 (CYP) 1A1/1A2/1B1 activity. Two variants of an extract from cultured Alternaria alternata, as well as the toxins alternariol (AOH), alternariol monomethyl ether (AME), altertoxin I (ATX-I), and altertoxin II (ATX-II), were tested singularly and in binary mixtures applying the 7-ethoxy-resorufin-O-deethylase (EROD) assay in MCF-7 breast cancer cells. Sub-cytotoxic concentrations of the two toxin mixtures, as well as ATX-I, ATX-II and AOH, exhibited dose-dependent enhancements of CYP 1 activity. ATX-I and ATX-II interacted synergistically in this respect, demonstrating the two perylene quinones as major contributors to the extract’s potential. Binary mixtures between AOH and the two altertoxins respectively exhibited concentration-dependent antagonistic as well as synergistic combinatory effects. Notably, AME showed no efficacy towards EROD enzyme activity or impact on other toxins’ efficacy. Hence, this study provides insights into synergistic and other combinatory effects of Alternaria toxins in natural co-occurrence scenarios in the context of AhR signalling pathway activation in breast cancer cells.
Highlights
The fungal species Alternaria alternata is known to infest crops including cereals, fruits, and vegetables [1,2]
EROD enzyme activity assay was conducted applying the complex mixtures of Alternaria toxins to test their potential to activate the aryl hydrocarbon receptor (AhR) signalling pathway
Significant enhancements in EROD activity were reached at concentrations of 20 μg/mL for both the complete extract” (CE) and the reduced extract” (RE), with a significantly higher induction observed for the RE (Figure 2a)
Summary
The fungal species Alternaria alternata is known to infest crops including cereals, fruits, and vegetables [1,2]. Frequent crop infestation by Alternaria spp., concomitant with simultaneous production of various secondary metabolites, as well as chemical stability during food processing and storage, results in persistent co-occurrence of Alternaria toxins [2,4,7,8,9]. A call by the European Food Safety Authority to collect further data on Alternaria toxins was followed by a rise in studies investigating nutritional exposure [1,2]. These uncovered co-contaminations of various Alternaria toxins in sunflower seed oil, tomato products, infant foods, and diverse fruit and vegetable juices [10,11,12]. A low abundance of AOH and AME was reported even in breast milk samples [13]
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