Impact of Alternaria toxins on CYP1A1 expression in different human tumor cells and relevance for genotoxicity

Pahlke, Gudrun; Tiessen, Christine; Domnanich, Katharina A.; Kahle, Nadine; Groh, Isabel Anna Maria; Schreck, Ilona; Weiss, Carsten; Marko, Doris

doi:10.1016/j.toxlet.2015.10.003

Cited by 28 publications

(40 citation statements)

References 40 publications

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“…Cytotoxicity of AOH was only marginal in LPS-stimulated THP-1 derived macrophages, which is in line with previous findings (Fig. 1a–d) (Pahlke et al 2016; Solhaug et al 2015, 2016; Tiessen et al 2013). In recent times, more and more light was shed on the mycotoxin AOH and its ability to manipulate the rich network of multiple biological processes needed to strategically mount a defense response.…”

Section: Discussionsupporting

confidence: 93%

The mycotoxin alternariol suppresses lipopolysaccharide-induced inflammation in THP-1 derived macrophages targeting the NF-κB signalling pathway

et al. 2018

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Alternariol (AOH) is a secondary metabolite formed by black mold of the genus Alternaria alternata. Due to limited hazard and occurrence data, AOH is still considered as an “emerging mycotoxin” and, as such, not monitored and regulated yet. Recent studies indicate immunosuppressive effects in vitro by altering the expression of CD molecules and proinflammatory cytokines, which are indispensable in mounting an innate immune response. However, the mode of action by which AOH exerts its immunosuppressive effects has not been unraveled yet. The present study aimed to characterise the impact of AOH on the nuclear factor kappa B (NF-κB) pathway, the expression of NF-κB target cytokines and involved regulatory microRNAs (miRNAs). In THP-1 derived macrophages, AOH (1–20 µM) was found to suppress lipopolysaccharide (LPS)-induced NF-κB pathway activation, decrease secretion of the proinflammatory cytokines IL-8, IL-6, TNF-α and to induce secretion of the anti-inflammatory IL-10. Thereby, a distinct pattern of cytokine mRNA levels was monitored, varying between short- and long-term exposure. Concomitantly, AOH (2–20 µM) affected the transcription levels of miR-146a and miR-155 in LPS-stimulated THP-1 derived macrophages dose-dependently by down- and upregulation, respectively. In contrast, transcription of miR-16 and miR-125b, two other immune-related miRNAs, was not modulated. In the absence of a LPS stimulus, AOH (20 µM) did not affect basal NF-κB activity, but increased IL-10 transcription. Collectively, our results indicate, that AOH itself does not induce a proinflammatory immune response in human macrophages; however, in an inflamed environment it possesses the ability to repress inflammation by targeting the NF-κB signalling pathway and regulatory miRNAs.

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Section: Discussionsupporting

confidence: 93%

The mycotoxin alternariol suppresses lipopolysaccharide-induced inflammation in THP-1 derived macrophages targeting the NF-κB signalling pathway

et al. 2018

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“…The hydroxylation of AOH and AME was studied under in vivo-like conditions in precision-cut rat liver slices of rats. The pattern of in vivo metabolites was comparable to that of in vitro metabolites of AOH, clearly supporting the relevance of an oxidative in vivo metabolism [20]. AOH and AME were extensively conjugated in suspension cultures of tobacco BY-2 cells, demonstrating that masked mycotoxins of AOH and AME can be formed in plant cells [51].…”

Section: Stability Of Alternaria Mycotoxins the Stability Ofsupporting

confidence: 63%

“…Moreover, AOH and AME were able to induce DNA strand break and gene mutations in cultured human and animal cells [18,19]. They interfered with the activity of human topoisomerases by affecting the stabilization of topoisomerase II-DNA-intermediates and the modulation of the redox balance in human colon carcinoma cells yet without any apparent negative impact on DNA integrity [20]. AOH and AME are frequently found in combination [21] as they share a common biosynthesis pathway [22].…”

Section: Toxicity Of Alternaria Mycotoxinsmentioning

confidence: 99%

“…Recently, high genotoxic potency of ATX II in both mammalian and human cells was demonstrated, and it was described as the most potent substance within the ATX group, capable of different mechanisms of action [34]. Nevertheless, data concerning the underlying modes of action are still limited [20].…”

Section: Toxicity Of Alternaria Mycotoxinsmentioning

confidence: 99%

“…After studying the absorption of four Alternaria toxins with perylenequinone structures in the Caco-2 cell Transwell system (a widely accepted in vitro model for human intestinal absorption and metabolism), it was shown that ATX I and ALTCH were not metabolized in Caco-2 cells, while ATX II and STE III were partly biotransformed by reductive deepoxidation to ATX I and ALTCH metabolites, respectively [54]. Very low ATX-II absorption and partial metabolism of ATX-I was observed in the intestinal Caco-2 Transwell system [20].…”

Section: Stability Of Alternaria Mycotoxins the Stability Ofmentioning

confidence: 99%

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AlternariaMycotoxins in Food and Feed: An Overview

Escrivá

Oueslati

Font

et al. 2017

Journal of Food Quality

131

116

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Alternaria is one of the major mycotoxigenic fungal genera with more than 70 reported metabolites. Alternaria mycotoxins showed notably toxicity, such as mutagenicity, carcinogenicity, induction of DNA strand break, sphingolipid metabolism disruption, or inhibition of enzymes activity and photophosphorylation. This review reports on the toxicity, stability, metabolism, current analytical methods, and prevalence of Alternaria mycotoxins in food and feed through the most recent published research. Half of the publications were focused on fruits, vegetables, and derived products-mainly tomato and apples-while cereals and cereal byproducts represented 38%. The most studied compounds were alternariol, alternariol methyl ether, tentoxin, and tenuazonic acid, but altenuene, altertoxins (I, II, and III), and macrosporin have been gaining importance in recent years. Solid-liquid extraction (50%) with acetonitrile or ethyl acetate was the most common extraction methodology, followed by QuEChERS and dilutiondirect injection (both 14%). High-and ultraperformance liquid chromatography coupled with tandem mass spectrometry was the predominant determination technique (80%). The highest levels of alternariol and alternariol methyl ether were found in lentils, oilseeds, tomatoes, carrots, juices, wines, and cereals. Tenuazonic acid highest levels were detected in cereals followed by beer, while alternariol, alternariol methyl ether, tenuazonic acid, and tentoxin were found in legumes, nuts, and oilseeds.

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Toxicokinetics of Mycotoxins

Singh

Kumari

2022

Mycotoxins and Mycotoxicoses

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Impact of Alternaria toxins on CYP1A1 expression in different human tumor cells and relevance for genotoxicity

Cited by 28 publications

References 40 publications

The mycotoxin alternariol suppresses lipopolysaccharide-induced inflammation in THP-1 derived macrophages targeting the NF-κB signalling pathway

The mycotoxin alternariol suppresses lipopolysaccharide-induced inflammation in THP-1 derived macrophages targeting the NF-κB signalling pathway

AlternariaMycotoxins in Food and Feed: An Overview

Toxicokinetics of Mycotoxins

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