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PubMedDate not supplied

The use of the chicken embryo screening test and brine shrimp (Artemia salina) bioassays to assess the toxicity of fumonisin B1 mycotoxin.

Chicken embryos and brine shrimp naulpii were utilized in short-term toxicity bioassays to assess their sensitivity to the mycotoxin fumonisin B1 (FB1). Fertile chicken eggs (Cobb x) were dosed with FB1 on day 2 of incubation by the injection of 100 microliters of aqueous solution into the air space of each egg. Eggs were incubated with mechanical rotation until hatch, at which time mortality was assessed. Probit transformation of the mortality data produced a linear line of best fit (P < 0.05), from which an LD50 of 52 micrograms FB1/egg, equivalent to a concentration of 1.3 microns hatched in artificial seawater and exposed to FB1 in an optimized 96-well plate assay with a 48 hr mortality endpoint. Probit transformation of the mortality data resulted in an LC50 of 1.7 microns FB1, or 1.2 micrograms FB1/ml. Thus, at the cellular level, both bioassays appeared sensitive to FB1; however, from the standpoint of use as a screening assay, the chicken embryo bioassay is limited by the relatively high dose of FB1 required per egg. It is anticipated that the design and simplicity of the brine shrimp bioassay will accommodate screening for FB1 toxicity in contaminated samples.

Animals↗
PubMedDate not supplied

Elimination and excretion of a single dose of the mycotoxin fumonisin B2 in a non-human primate.

The mycotoxin fumonisin B2 (FB2), which can be present at significant levels in maize infected with the fungus Fusarium moniliforme, was dosed both iv and by gavage to vervet monkeys. It was rapidly eliminated from the plasma of vervet monkeys dosed i.v. with 2 mg FB2/kg body mass. The concentration of FB2 in plasma after the iv dose was characterized by an initial distributional phase and a subsequent elimination phase with a mean half-life of 18 min. When two monkeys were dosed by gavage with a single bolus (7.5 mg/kg body mass), only one showed detectable trace levels of FB2 in plasma (25-40 ng/ml over the 3-5 hr period after dosing). This indicates that, like FB1, FB2 has a limited bioavailability. Urinary excretion of FB2 was extremely low, even after i.v. dosing. In total, a mean of 4.1% of the i.v. dose and 0.2% of the gavage dose was recovered in urine over a 7-day period. The predominant route of excretion was via the faeces, mainly as the unmetabolized toxin or as a partially hydrolysed analogue, with the latter accounting for between 6% and 47% of the dose. Limited amounts (maximum of 1.1%) of the fully hydrolysed aminopolyol backbone of FB2 were recovered in faeces.

Animals↗
PubMed1999

The mycotoxin fumonisin B1 inhibits integrin-mediated cell-matrix adhesion.

Fumonisin B1 (FB1), a mycotoxin produced by the corn fungus Fusarium moniliforme, causes a variety of animal diseases and is a suspected human carcinogen. The FB1 molecule bears remarkable structural resemblance to the long-chain sphingoid base backbones of sphingolipids. The toxicity and carcinogenicity of FB1 has been ascribed to its ability to inhibit ceramide synthase, a key enzyme in the metabolism of complex sphingolipids. In this study we have investigated whether the exposure of B16-BL6 mouse melanoma cells to FB1 affects cell growth and integrin-mediated cell matrix adhesion. Cell treatment with the highest tested dose (75 microM) of FB1 for 72 h induced an about 20% inhibition of cell growth. FB1 strongly affected B16-BL6 cell adhesion to immobilized fibronectin, by causing a dose-dependent inhibition of cell attachment to this substrate. FB1 also inhibited in a dose-dependent manner the adhesion of B16-BL6 cells to the immobilized anti-fibronectin receptor antibody, whereas it affected only to a low extent cell attachment to concanavalin A. Our results demonstrate that FB1 treatment alters integrin adhesive activity, thus affecting all cellular integrin-dependent functions.

Animals↗
PubMed1997

Retinol, ascorbic acid and alpha-tocopherol prevent DNA adduct formation in mice treated with the mycotoxins ochratoxin A and zearalenone.

Ochratoxin A (OTA), and zearalenone (ZEN), two mycotoxins, have been implicated in numerous mycotoxicoses in farm animals and are genotoxic. Several adducts were detected in mouse and rat kidney after a single administration of OTA and in mice organs after zearalenone treatment which induces hepatocellular adenomas. The effects of some vitamins such as retinol (A), ascorbic acid (C) and alpha-tocopherol (E), which are known to act as superoxide anion scavengers, were tested on OTA genotoxicity. Pretreatment of mice by vitamin E decreased DNA adducts by 80% in kidney. Vitamin A decreased DNA adduct levels by 70% and Vitamin C by 90% in kidney. In the same way, pretreatment of female mice with alpha-tocopherol before administration of zearalenone inhibited significantly DNA adduct formation in liver and in kidney. The total DNA adduct level after E treatment was decreased by 45% and 58% in liver and kidney respectively.

Animals↗
PubMedDate not supplied

Influence of the mycotoxins alpha- and beta-zearalenol and deoxynivalenol on the cell cycle of cultured porcine endometrial cells.

The present study investigated the effects of the mycotoxins alpha-zearalenol (alpha-ZOL) and beta-zearalenol (beta-ZOL) at concentrations of 7.5, 15, and 30 microM, and deoxynivalenol (DON) at concentrations of 0.94, 1.88, and 3.76 microM on cell cycle distribution (propidium iodide, PI staining) in combination with the proliferating cell nuclear antigen (PCNA) by flow cytometry. The viability of porcine uterine cells was not impaired at 30 microM alpha-ZOL, whereas beta-ZOL at this concentration and 3.76 microM DON significantly decreased cell number. Some cells showed ultrastructural features of cell death indicated by swollen mitochondria, disrupted cell membranes, and many vacuoles. After 24 and 48h of exposure to alpha-ZOL (7.5, 15, or 30 microM), the cell cycle distribution was still comparable to the control groups. An anti-proliferative effect of beta-ZOL and DON was detected by a significant reduction in the S-phase together with arrest of cells in the G(0)/G(1)-phase. The results show that beta-ZOL (7.5, 15, or 30 microM) and DON (0.94, 1.88, or 3.76 microM) control the progression of cells through the cycle by decreasing S-phase and arresting cells in the G(0)/G(1)-phase of the cell cycle. A significant decrease in the expression of the proliferation marker PCNA amounts indicates that beta-ZOL and DON disengaged cells from active cycling. We confirm that alpha-ZOL possesses a relative binding affinity to porcine uterine cytoplasmic estrogen receptor.

Animals↗
PubMed1993

Tremorgenic encephalopathy: a role of mycotoxins in the production of CNS disease in humans?

We describe a young man who, shortly after exposure to moldy silage, developed a neurological syndrome consisting of dementia and a remarkable tremor which was precipitated by movement. All symptoms resolved within one week. Despite investigation, no definitive diagnosis was reached. We propose that this patient's illness may have resulted from inhalation exposure to a tremorgenic mycotoxin.

Adolescent↗
PubMed2001

Molecular dynamics simulations on the mycotoxin fumonisin B1.

The solution conformational properties of the mycotoxin fumonisin B(1) have been studied using molecular dynamics methodology. Fumonisins have been shown to inhibit sphinganine (sphingosine) N-acyltransferase (ceramide synthase) and show a wide range of toxic effects in many animals. This study of the solution properties of fumonisin B(1) attempts to add to the structural models necessary for the understanding of the binding and activity properties. The computational method uses a box with periodic boundaries, filled with explicit TIP3P water molecules, the substrate fumonisin B(1), and selected counterions for charge neutrality. The starting structure of fumonisin B(1) is added to the box by excluding water molecules. The explicit image method using 12-A cutoffs is applied to the system and molecular dynamics are carried out on different starting conformations at 300 K in 100-picosecond (ps) steps. Examination of the resulting equilibrated conformations suggests that the structure is relatively extended and that previous computational studies in vacuo, showing a compact folded structure, may not be consistent with the solution structure.

Acyltransferases↗
PubMed2004

Analysis of the Fusarium mycotoxins fusaproliferin and trichothecenes in grains using gas chromatography-mass spectrometry.

A method is described using gas chromatography-mass spectrometry (GC-MS) for the simultaneous detection of the Fusarium mycotoxins fusaproliferin and seven trichothecenes from grains. Sample purification of the raw extract was carried out with commercial solid phase extraction columns, and the recovery of the more polar analytes was increased by rinsing the column with acetonitrile. A significant matrix effect was found for the analysis of fusaproliferin and trichothecenes; thus, the calibrants should be prepared in a blank matrix. The response was linear in the range used. The mean recovery for fusaproliferin was 60.4 or 62.9%, depending on the spiking level. With respect to the trichothecenes, the recovery was generally higher (70.2-125.3%). The method proved to be repeatable for the analysis of fusaproliferin and trichothecenes. The limit of detection for fusaproliferin in the blank matrix mixture was 50 microg/kg, and that for trichothecenes was 5-15 microg/kg. Thirty-eight Finnish grain samples were analyzed for fusaproliferin and trichothecenes with the method developed. Fusaproliferin was not detected in any of the samples. The mean levels of deoxynivalenol, 3-acetyldeoxynivalenol, nivalenol, HT-2 toxin, and T-2 toxin in Finnish grain samples were 272, 17, 150, 40, and <20 microg/kg, respectively.

Edible Grain↗
PubMed2006

Mycotoxin contamination of dietary and medicinal wild plants in the Eastern Cape Province of South Africa.

Nineteen dietary and 30 medicinal wild plants used by residents of the Eastern Cape Province of South Africa were investigated for the presence of fumonisin B1 and aflatoxin B1. The plants were extracted in water, and cleanup was undertaken on immunoaffinity cartridges; analysis was by HPLC using fluorescence detection. None of the plant extracts contained detectable levels of aflatoxin B1; however, eight plants, four dietary and four medicinal, were positive for fumonisin B1 at levels ranging from 34 to 524 microg/kg and from 8 to 1553 microg/kg, respectively. The presence of fumonisin B1 was confirmed by LC-MS/MS using positive ion electrospray ionization. Fumonisin B1 provided characteristic fragment ions at m/z 704, 686, 546, 528, 370, and 352 corresponding to sequential loss of H2O and tricarboxylic acid moieties from the alkyl backbone. These results indicate that exposure to fumonisin B1 is much more widespread than initially thought and is the first report of mycotoxin contamination in South African medicinal and dietary wild plants.

Aflatoxin B1↗
PubMed1999

Quantification of the mycotoxin patulin by a stable isotope dilution assay.

Two stable isotope dilution assays for the quantification of patulin [4-hydroxy-4H-furo[3,2-c]pyran-2(6H)-one] in foods were developed using (13)C-labeled patulin as the internal standard. One method was performed by means of LC/MS in negative electrospray ionization mode without derivatization; the other used HRGC/HRMS after trimethylsilylation of the patulin isotopomers. In comparison with previously reported methods based on high-performance liquid chromatography with UV detection, HRGC/HRMS of the derivatized samples showed better repeatability, higher recovery rates (96% at a spike level of 200 ng/L), and a 100 times lower detection limit (12 ng/L). In contrast, LC/MS showed a much lower performance as compared to HPLC/UV or HRGC/HRMS. Using HRGC/HRMS, the mycotoxin was quantified in many different fruit products and in molded wheat bread.

Beverages↗
PubMedDate not supplied

Mycotoxin production and cytotoxicity of Fusarium strains isolated from Norwegian cereals.

Thirty-four isolates of the eight most common Fusarium species isolated from Norwegian cereals; F. avenaceum, F. culmorum, F. equiseti, F. graminearum, F. poae, F. sporotrichioides, F. torulosum and F. tricinctum were studied for their cytotoxicity and ability to produce mycotoxins. The strains were cultivated on rice, and analysed for trichothecenes (all species), zearalenone (all species), fusarochromanone (F. equiseti), wortmannin (F. torulosum), moniliformin and enniatins (F. avenaceum, F. tricinctum and F. torulosum). The cytotoxicity of the extracts were examined with an (in vitro) MTT-cell culture assay. All F. graminearum and five of seven F. culmorum isolates belonged to chemotype IA, producing deoxynivalenol and 3-acetyl-deoxynivalenol, while the two other F. culmorum strains were nivalenol producers (chemotype II). The F. equiseti isolates and one of the F. poae isolates produced both type A and B trichothecenes, and relatively large quantities of fusarochromanone were detected in the F. equiseti cultures. All Fusarium species studied showed significant cytotoxicity, but with a large variation between species, and also within each species. F. sporotrichioides and F. equiseti showed the highest average cytotoxicity.

Androstadienes↗
PubMed1999

Mycoflora and mycotoxins of Brazilian cashew kernels.

Kernel samples of common and dwarf Brazilian cashew nuts were highly contaminated with field and storage fungi in comparison to healthy ones. In general, dwarf cashews were more contaminated than common. A total of 37 fungal species were identified. Aspergillus niger was the dominant species with more colonies being isolated from dwarf kernels. A. flavus was the next most frequently isolated species. Penicillium brevicompactum, and P. glabrum were the most frequently isolated penicillia, with higher contamination recorded from dwarf kernels. Chaetomium globosum was recorded at a high level. Nine species were recorded from cashew kernels for the first time. Multimycotoxin analysis by tlc and hplc were positive for mycotoxins and other secondary metabolites particularly from the infected samples. Hplc was only carried out on dwarf cashews. Aflatoxins were not detected by quantitative high performance thin layer chromatography.

Aflatoxins↗
PubMed1999

Phytotoxicity of pathogenic fungi and their mycotoxins to cereal seedling viability.

Aspergillus flavus, Alternaria alternata and Fusarium oxysporum were the pathogenic fungi most reduced cereal (barley, sorghum and wheat) seedlings. The pathogens have the ability to produce aflatoxin B1 and G1, diacetoxyscirpenol, kojic acid and tenuazonic acid that reduced seedling viability. The inhibition dose for 50% reduction (LD50) was recorded by aflatoxins at 0.83 mg L-1 for barley, 1.74 mg L-1 for wheat and 2.75 mg L-1 for sorghum. Diacetoxyscirpenol produced its inhibition at 1.26 mg L-1 for barley, 3.98 mg L-1 for wheat and 10 mg L-1 for sorghum. Kojic acid induced 50% inhibition at 63 mg L-1 for barley, 105 mg L-1 for wheat and 251 mg L-1 for sorghum. However, tenuazonic acid was less toxic where the toxicity ranged between 79-550 mg L-1. The germination inhibition was more pronounced in barley followed by wheat and was negligible in sorghum for all tested mycotoxins. This inhibition was attributed to the reduction in the seedling amylase activity, where amylase was also reduced in the same trend: barley > wheat > sorghum. Grain treated with carboxin-captan and thiophanatemethyl-thiram at 1 g kg-1 grain increased the seedlings vigour of wheat in sterilized soil by 45 and 22%, barley by 24 and 33% and sorghum by 15 and 30%, respectively. These fungicides also had a positive effect on cereal when the soil was inoculated with A. flavus, A. alternata and F. oxysporum, but the improvement was still below normal.

Amylases↗
PubMed2001

A molecular imprinted polymer with recognition properties towards the carcinogenic mycotoxin ochratoxin A.

A molecularly imprinted polymer which recognises the mycotoxin ochratoxin A was prepared using the mimic N-(4-chloro-1-hydroxy-2-naphthoylamido)-(L)-phenylalanine as a template. The polymer was obtained by dissolving the template, methacrylic acid and ethylendimethacrylate in chloroform and polymerising the mixture by thermal treatment at 60 degrees C. The monolith obtained was crushed, sieved to 30-90 microm and extensively washed till the template could no longer be found in the washing solution. The binding properties towards the template, ochratoxin A and several related molecules were measured by eluting with acetonitrile and chloroform a HPLC column packed with the imprinted polymer. The experimental results show that the polymer recognises not only the template well, but also the ochratoxin A. The specific molecular recognition effect is due to hydrogen bond interactions but in order to assure the full recognition effect adjunctive steric factors are necessary. The magnitude of these interactions can be controlled by the use of limited amounts of acetic acid in the mobile phase. From the measurement of the relative selectivity it was found that only the simultaneous presence of the carboxyl, the phenolic hydroxyl and certain peculiar substructures such as the chlorine atom assures the whole recognition of the template.

Carcinogens↗
PubMed2003

A novel technique to evaluate interactions between Saccharomyces cerevisiae cell wall and mycotoxins: application to zearalenone.

Three models based on sigmoidal plotting were tested for their ability to describe zearalenone adsorption on Saccharomyces cerevisiae cell walls in vitro. All three models closely fitted the experimental data, but Hill's equation gave the most accurate parameters, and provided information on the physical and chemical mechanisms involved in the adsorption of mycotoxin on yeast cell walls.

Adsorption↗
PubMed1983

An intermediary role for the tremorgenic mycotoxin TR-2 in the biosynthesis of verruculogen.

14C-Labelled compound TR-2, a tremorgenic mycotoxin, was administered to Penicillium raistrickii in submerged fermentation. Half of the added radiolabel was taken up by the fungus during the 60 h incubation period and the secondary metabolites subsequently isolated, principally verruculogen but also fumitremorgin B, were found to be radiolabelled. The efficiency of biosynthetic incorporation of TR-2 into verruculogen within the mycelium was at least 35%, demonstrating for the first time an intermediary role for TR-2. Fumitremorgin B was also TR-2-derived but may not be an important intermediate in verruculogen biosynthesis.

Chemical Phenomena↗
PubMed1984

Chemical carcinogenesis: mycotoxins and other chemicals to which humans are exposed.

HCC occurs in a higher incidence in some subsets of human populations residing in specific geographic areas around the world. These include black populations residing south of the Sahara, particularly in South and East Africa; in populations of Southeast Asia and the Western Pacific; in India, China, and in some other circumscribed areas. These epidemiologic observations strongly suggest that environmental factors are involved in the etiology of HCC. Evidence from human and animal data point toward a multicausal etiology, including dietary or environmental contamination with mycotoxin carcinogens, acting in concert with hepatitis B viral infection and, in some areas, with malnutrition. Dietary factors that appear to influence susceptibility to HCC include fat, protein and amino acids, vitamin A, selenium, and zinc. In addition, alcohol consumption, environmental chemicals that are natural or man made, and genetic predisposition must also be considered. It seems likely that identification of etiologic agents (hepatitis B infection, aflatoxin, malnutrition) and correction or prevention of these are the most promising means for controlling HCC in man.

Aflatoxins↗