Disease relevance of ZEARALENONE

• Zearalenone is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium which colonize maize, barley, oats, wheat and sorghum and have been implicated in numerous mycotoxicoses in farm animals, especially pigs [1].
• These results confirm the genotoxicity of zearalenone and its ability to induce hepatocellular adenomas, rather than tumours of genital organs, in mice [1].
• Zearalenone was found to be negative in the Salmonella typhimurium assay [1].
• However, zearalenone and its estrogenic metabolites showed a positive DNA damaging effect in recombination tests with Bacillus subtilis [1].
• The negative mutagenicity of the four other 12,13-epoxytrichothecenes tested, and of zearalenone and moniliformin, could not be correlated with in vivo tests because published accounts of their chronic toxicity were not available [2].

Psychiatry related information on ZEARALENONE

• Days 7 to 10 postmating seem to be a critical period of gestation for zearalenone to exert its detrimental actions on early embryonic development [3].

High impact information on ZEARALENONE

• Precocious sexual development in Puerto Rico and oestrogenic mycotoxins (zearalenone) [4].
• In this review we report the use of mass spectrometry in connection with chromatographic techniques for mycotoxin determination by considering separately the most diffuse class of mycotoxins: patulin, aflatoxins, ochratoxin A, zearalenone, trichothecenes, and fumonisins [5].
• The estrogenic effect of zearalenone derivatives was investigated for their binding characteristics to cytosol and nuclear receptors in the uterus [6].
• In particular, two inhibitors of the plasma membrane proton pump, diethylstilbestrol and zearalenone, had been shown to be stalk cell inducers [7].
• Antiestrogenic activity of the phytoestrogens could not be detected, except for zearalenone which is a full agonist for ER alpha and a mixed agonist-antagonist for ER beta [8].

Chemical compound and disease context of ZEARALENONE

• Genistein and the fungal toxin zearalenone were found to increase the activity of cyclin dependent kinase 2 (Cdk2) and cyclin D1 synthesis and stimulate the hyperphosphorylation of the retinoblastoma susceptibility gene product pRb105 in MCF-7 cells [9].
• We inactivated zes2, the gene encoding zearalenone lactonase in G. roseum, by inserting a hygromycin resistance cassette into the coding sequence of the gene by means of Agrobacterium tumefaciens-mediated genetic transformation [10].
• Ochratoxin A (OTA) and zearalenone (ZEA), two naturally occurring contaminants of animal feed, have been implicated in several mycotoxicoses in farm livestock but there is little information on their genotoxicity and toxicity in these species [11].
• Epidemiological, clinical and histological findings (when available) in outbreaks of mycotoxicoses resulting from exposure to aflatoxins, ergot, trichothecenes, ochratoxins, 3-nitropropionic acid, zearalenone and fumonisins are discussed [12].
• Our data clearly shows that oxidative stress is certainly involved in the toxicity of the three studied mycotoxins, Citrinin, Zearalenone and T2 toxin and may therefore constitutes a relevant part in their toxicities; however, at variable extent from one mycotoxin to another [13].

Biological context of ZEARALENONE

• Signal transduction through the Ras/Erk pathway is essential for the mycoestrogen zearalenone-induced cell-cycle progression in MCF-7 cells [14].
• In the rat uterus enlargement bioassay, the metabolite or its hydrolysis product was found to retain the estrogenic activity characteristic of zearalenone [15].
• In addition, zearalenone functioned as an antiapoptotic agent by increasing the survival of MCF-7 cell cultures undergoing apoptosis caused by serum withdrawal [14].
• Downregulation of p27(KIP1) proceeded in p16(INK4A)-expressing cells after zearalenone treatment, and G(1) arrest afforded by p16(INK4A) expression was reversible upon prolonged treatment with zearalenone [16].
• Estrogen-controlled gene expression in tissue culture cells by zearalenone [17].

Anatomical context of ZEARALENONE

• Due to the high sensitivity of these cell lines for zearalenone both test systems are proposed as assays for a quantitative estimation of the biological (estrogenic) activity of this widespread mycotoxin [17].
• Due to the unavailability of an analytical standard, the ZON-4-O-Glc is not measured in routine analytical procedures, even though it can be converted back to active zearalenone in the digestive tracts of animals [18].
• The concentration of oestrogen receptor (ER) binding sites after the DMBA treatment was low in the mammary glands of all groups but a significantly higher proportion of the glands in the zearalenone exposed rats were ER-positive (i.e. ER levels > or = 5 fmol mg(-1) protein) than the glands of the vehicle controls [19].
• 3H- and 14C-labeled zearalenone were found to bind preferentially to one of two peaks containing uncharacterized proteins obtained from the cytosol of young mycelium and resolved by gel column chromatography [20].
• We have investigated interactions between five mycotoxin species (Trichothecenes, Fumonisins, and Zearalenone) using the DNA synthesis inhibition assay in L929 fibroblasts [21].

Associations of ZEARALENONE with other chemical compounds

• Metabolism of ochratoxin A, zearalenone, and diacetoxyscirpenol was moderately or slightly inhibited by addition of milled feed in vitro [22].
• Zearalenol, the reduction product of zearalenone produced by Fusarium roseum growing in cereals, was found for the first time naturally occurring in oats and corn [23].
• The estrogenic activity of the mycotoxin zearalenone (ZEA) and its metabolites [alpha]-ZEA) and ss-zearalenol (ss-ZEA)], with regard to zonagenesis and vitellogenesis, was assessed in this assay system [24].
• In two estrogen-sensitive cell lines, Le42 and MCF-7, the estrogenic potential of the nonsteroidal mycotoxin zearalenone has been investigated [17].
• Radioimmunoassay for zearalenone and zearalanol in human serum: production, properties, and use of porcine antibodies [25].

Gene context of ZEARALENONE

• Cdk inhibitory activity in lysates of zearalenone-treated cells was depleted by anti-p27(KIP1) and anti-Cdc2 interacting protein (p21(CIP1)) antibodies [16].
• Treatment of hPXR-transduced cultured hepatocytes isolated from PXR-knockout mice with zearalenone induces the expression of Cyp3a11, the prototypical murine hepatic PXR-target gene [26].
• We demonstrated that zearalenone could stimulate the growth of estrogen receptor-positive human breast carcinoma cell line MCF-7 [14].
• At sub-micromolar concentrations genistein, daidzein, and zearalenone stimulated ERalpha and ERbeta-dependent transcription in Neuro2A cells co-transfected with ERs and simple and complex estrogen-response-element (ERE) containing promoters, although compounds were more active in the presence of ERbeta [27].
• Cell walls of strains wt292 and mnn9, which have higher levels of beta-D-glucans, were able to complex larger amounts of zearalenone, with higher association constants and higher affinity rates than those of the fks1 and sc1026 strains [28].

Analytical, diagnostic and therapeutic context of ZEARALENONE

• Determination of zearalenone in corn by laser fluorimetry [29].
• Indirect enzyme-linked immunosorbent assay for the mycotoxin zearalenone [30].
• Sixteen Fusarium isolates belonging to F. graminearium Schw. and F. culmorum (W.G. Smith) Sacc. produced vomitoxin and zearalenone on cracked corn at 28 degrees C. Quantitation for vomitoxin was by gas-liquid chromatography [31].
• A sensitive and inexpensive yeast bioassay for the mycotoxin zearalenone and other compounds with estrogenic activity [32].
• The inhibitory effects of zearalenone analogs observed in the blastogenesis assay did not correlate with the estrogenic potencies of these compounds [33].

References