Mutagenicity of the mycotoxin alternariol in cultured mammalian cells

Brugger, Eva-Maria; Wagner, Jörg; Schumacher, David M.; Koch, K. M.; Podlech, Joachim; Metzler, Manfred; Lehmann, Leane

doi:10.1016/j.toxlet.2006.01.001

Cited by 170 publications

(112 citation statements)

References 17 publications

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“…AME and AOH were not very acutely toxic; however, they do exert genotoxic, mutagenic, and carcinogenic properties and show remarkable cytotoxicity in microbial and mammalian cell culture. 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].…”

Section: Toxicity Of Alternaria Mycotoxinsmentioning

confidence: 99%

AlternariaMycotoxins in Food and Feed: An Overview

Escrivá

Oueslati

Font

et al. 2017

Journal of Food Quality

146

127

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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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Section: Toxicity Of Alternaria Mycotoxinsmentioning

confidence: 99%

AlternariaMycotoxins in Food and Feed: An Overview

Escrivá

Oueslati

Font

et al. 2017

Journal of Food Quality

146

127

View full text Add to dashboard Cite

show abstract

“…The two mycotoxins are common contaminants of food such as grain and grain-based products, fruits/fruit juice, and vegetable products (in particular, tomato products) (21)(22)(23). They have been reported to exhibit cytotoxic, fetotoxic, teratogenic, and possible mutagenic and estrogenic effects (24)(25)(26)(27) and may contribute to development of human esophageal cancer (28). AOH has been demonstrated to inhibit cholinesterase (29) and topoisomerases I and II (30).…”

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confidence: 99%

SnPKS19 Encodes the Polyketide Synthase for Alternariol Mycotoxin Biosynthesis in the Wheat Pathogen Parastagonospora nodorum

Chooi

Muria-Gonzalez

Mead

et al. 2015

Appl Environ Microbiol

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b Alternariol (AOH) is an important mycotoxin from the Alternaria fungi. AOH was detected for the first time in the wheat pathogen Parastagonospora nodorum in a recent study. Here, we exploited reverse genetics to demonstrate that SNOG_15829 (SnPKS19), a close homolog of Penicillium aethiopicum norlichexanthone (NLX) synthase gene gsfA, is required for AOH production. We further validate that SnPKS19 is solely responsible for AOH production by heterologous expression in Aspergillus nidulans. The expression profile of SnPKS19 based on previous P. nodorum microarray data correlated with the presence of AOH in vitro and its absence in planta. Subsequent characterization of the ⌬SnPKS19 mutants showed that SnPKS19 and AOH are not involved in virulence and oxidative stress tolerance. Identification and characterization of the P. nodorum SnPKS19 cast light on a possible alternative AOH synthase gene in Alternaria alternata and allowed us to survey the distribution of AOH synthase genes in other fungal genomes. We further demonstrate that phylogenetic analysis could be used to differentiate between AOH synthases and the closely related NLX synthases. This study provides the basis for studying the genetic regulation of AOH production and for development of molecular diagnostic methods for detecting AOH-producing fungi in the future.

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“…alternata is a widespread saprophytic species which produces a wide variety of different secondary metabolites, among which are the mutagenic mycotoxins alternariol (AOH) and altertoxin (ATX) (2)(3)(4). For AOH and its monomethylether (AME), it has been shown recently that they have potential to cause DNA double-strand breaks in mammalian cells in vitro (5).…”

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confidence: 99%

Role of the Alternaria alternata Blue-Light Receptor LreA (White-Collar 1) in Spore Formation and Secondary Metabolism

Pruß

Fetzner

Seither

et al. 2014

Appl Environ Microbiol

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Alternaria alternata is a filamentous fungus that causes considerable loss of crops of economically important feed and food worldwide. It produces more than 60 different secondary metabolites, among which alternariol (AOH) and altertoxin (ATX) are the most important mycotoxins. We found that mycotoxin production and spore formation are regulated by light in opposite ways. Whereas spore formation was largely decreased under light conditions, the production of AOH was stimulated 2-to 3-fold. ATX production was even strictly dependent on light. All light effects observed could be triggered by blue light, whereas red light had only a minor effect. Inhibition of spore formation by light was reversible after 1 day of incubation in the dark. We identified orthologues of genes encoding the Neurospora crassa blue-light-perceiving white-collar proteins, a cryptochrome, a phytochrome, and an opsin-related protein in the genome of A. alternata. Deletion of the white-collar 1 (WC-1) gene (lreA) resulted in derepression of spore formation in dark and in light. ATX formation was strongly induced in the dark in the lreA mutant, suggesting a repressing function of LreA, which appears to be released in the wild type after blue-light exposure. In addition, light induction of AOH formation was partially dependent on LreA, suggesting also an activating function. A. alternata ⌬lreA was still able to partially respond to blue light, indicating the action of another blue-light receptor system.

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Mutagenicity of the mycotoxin alternariol in cultured mammalian cells

Cited by 170 publications

References 17 publications

AlternariaMycotoxins in Food and Feed: An Overview

AlternariaMycotoxins in Food and Feed: An Overview

SnPKS19 Encodes the Polyketide Synthase for Alternariol Mycotoxin Biosynthesis in the Wheat Pathogen Parastagonospora nodorum

Role of the Alternaria alternata Blue-Light Receptor LreA (White-Collar 1) in Spore Formation and Secondary Metabolism

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