Structure-activity relationships for human estrogenic activity in zearalenone mycotoxins

Shier, W. Thomas; Shier, Anna C.; Xie, Weiping; Mirocha, C. J.

doi:10.1016/s0041-0101(00)00259-2

Cited by 267 publications

(170 citation statements)

References 20 publications

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“…The higher potency of α-ZOL and α-ZAL as compared to parent ZEA and β-ZOL, reflect their higher affinity to the oestrogen receptors in MCF-7 cells. These findings were in accordance with previous results, demonstrating that in a conventional eutopic assay, which assesses the increase of the organ weight of the juvenile uterus in mice or rats, the same ranking of the oestrogenic effects of ZEA and its metabolites was observed [35,40].…”

Section: Discussionsupporting

confidence: 93%

Bioactivation of zearalenone by porcine hepatic biotransformation

2005

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-Zearalenone (ZEA) is a resorcylic acid lactone derivative produced by various Fusarium species that are widely found in food and feeds. The structure of zearalenone is flexible enough to allow a conformation able to bind to mammalian oestrogen receptors, where it acts as an agonist. Using oestrogen-dependent Human Breast Cancer (MCF-7) cells, the oestrogenic activity of zearalenone and its derivatives were compared using 17 β-oestradiol as a positive control. The results obtained demonstrate that the oestrogenic potency of ZEA derivatives could be ranked in the following order: α-zearalenol > α-zearalanol > zearalenone > β-zearalenol. Since pigs have been reported to be among the most sensitive animal species, biotransformation studies with pig liver subcellular fractions were conducted. These studies indicated that α-zearalenol is the main hepatic metabolite of zearalenone in pigs, and it is assumed that 3α-and 3β-hydroxysteroid dehydrogeneases are involved in the hepatic biotransformation, since the formation of α-zearalenol and β-zearalenol could be inhibited by prototypic substrates for either enzyme. The bioactivation of ZEA into the more active α-zearalenol seems to provide a possible explanation for the observed high sensitivity of pigs towards feedingstuffs contaminated with the mycotoxin. zearalenone / MCF-7 cells / oestrogenic effects / biotransformation / pigs

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Section: Discussionsupporting

confidence: 93%

Bioactivation of zearalenone by porcine hepatic biotransformation

2005

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“…The carcinogenicity of ZEA has not been established, and IARC has classified it in group 3 (25). However, ZEA levels reported in cornfl akes (13.0 µg kg -1 to 20.0 µg kg -1 ) stimulated proliferation of human carcinoma breast cells MCF7 (26), which suggests that ZEA could have a role in the development of breast cancer in women. Furthermore, ZEA contamination of maize products was associated with precocious sexual development (19).…”

Section: Discussionmentioning

confidence: 97%

Co-occurrence of Aflatoxins, Ochratoxin A, Fumonisins, and Zearalenone in Cereals and Feed, Determined by Competitive Direct Enzyme-Linked Immunosorbent Assay and Thin-Layer Chromatography

Klarić

Cvetnić

Pepeljnjak

et al. 2009

Archives of Industrial Hygiene and Toxicology

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Aspergillus, Penicillium, and Fusarium species frequently contaminate crops. For this reason mycotoxins such as afl atoxins (AFs), ochratoxin A (OTA), fumonisins (FBs), and zearalenone (ZEA) are found in food and feed in a wide range of concentrations, depending on environmental and storage conditions. Consumption of mycotoxin-contaminated food and feed has been associated with acute and chronic poisoning and carcinoma. The aim of this study was to determine the incidence and co-occurrence of AFs (B 1 +B 2 +G 1 +G 2 ), OTA, FBs (B 1 +B 2 +B 3 ), and ZEA in 37 samples of cereals and feed randomly collected in 2007 from households of an endemic nephropathy (EN) area in Croatia. The mycotoxins were determined using the competitive direct ELISA test (CD-ELISA) in combination with thin-layer chromatography (TLC). The most frequent mycotoxin was ZEA (92 %, mean 318.3 µg kg -1 ), followed by FBs (27 %, 3690 µg kg -1 ), AFs (24.3 %, 4.6 µg kg -1 ), and OTA (16.2 %, 9.8 µg kg -1 ). Levels of AFs, ZEA, and FBs detected by CD-ELISA signifi cantly correlated with the TLC results. However, only one OTA-positive sample was confi rmed by TLC due to its high limit of detection. The levels of these mycotoxins were below the permissible limit for animal feed. Twenty-nine percent of cereals were contaminated with FBs, OTA, or ZEA in mass fractions above the permissible limit for humans. Co-occurrence of two toxins varied between 4.2 % and 54 % and of three between 4.2 % and 7.6 %. Prolonged co-exposure to AFs, OTA, FBs, and ZEA might increase the risk of various chronic diseases.

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“…The observed reduction in ZON after the temperature shift might be due to a modification of ZON to a ZON derivative or because ZON was degraded by the fungus itself during growth. The ELISA kit employed in this study used monoclonal antibodies, and was not designed to detect the many different ZON derivatives (Shier et al 2001), so any derivative or degradation product would not have been detected. In another experiment, the expression levels of the four known ZON genes showed tendencies to a cyclic wavelike pattern over time when grown on sterile rice at constant 25°C (Lysoe et al, 2008, submitted).…”

Section: Discussionmentioning

confidence: 99%

Identification of up-regulated genes during zearalenone biosynthesis in Fusarium

Lysøe

Bone²,

Klemsdal³

2008

Eur J Plant Pathol

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The Fusarium genus includes devastating plant pathogenic fungi that cause diseases in cereals around the world. They produce several mycotoxins, including the estrogenic compound zearalenone. To better understand the molecular mechanisms determining zearalenone production, we performed differential display RT-PCR under conditions where Fusarium graminearum and F. culmorum produced high amounts of zearalenone. We found 133 expressed sequence tags (ESTs) and 54 of these were considered to be up-regulated during high zearalenone production. Several of the ESTs were confirmed to be up-regulated by real-time qPCR, but none showed any significant down-regulation in the zearalenone negative mutant ΔPKS4-T9, or were similar to typical gene expression patterns of previously described zearalenone-related genes. Some of the up-regulated ESTs were similar to genes involved in secondary metabolite production, lipid metabolism, transcriptional activation, provision of precursors, signal transduction, transport or detoxification. Several of the ESTs were also located adjacent to one another in the genome and therefore might represent genes involved in the same biosynthetic pathway. Members of six such putative pathways could be found. All sequences were compared to the MIPS F. graminearum Genome Database to verify autocalled gene predictions experimentally and to introduce new exons and gene structures.

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Structure-activity relationships for human estrogenic activity in zearalenone mycotoxins

Cited by 267 publications

References 20 publications

Bioactivation of zearalenone by porcine hepatic biotransformation

Bioactivation of zearalenone by porcine hepatic biotransformation

Co-occurrence of Aflatoxins, Ochratoxin A, Fumonisins, and Zearalenone in Cereals and Feed, Determined by Competitive Direct Enzyme-Linked Immunosorbent Assay and Thin-Layer Chromatography

Identification of up-regulated genes during zearalenone biosynthesis in Fusarium

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