Fumonisin B1

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Fumonisin B1
Fumonisin B1.svg
Names
Preferred IUPAC name
(2S,2′S)-2,2′-[(5S,6R,7R,9R,11S,16R,18S,19S)-19-Amino-11,16,18-trihydroxy-5,9-dimethylicosane-6,7-diyl]bis[oxy(2-oxoethane-2,1-diyl)]dibutanedioic acid
Other names
Macrofusine
Identifiers
3D model (JSmol)
ECHA InfoCard 100.150.289 OOjs UI icon edit-ltr-progressive.svg
KEGG
PubChem CID
UNII
  • InChI=1/C34H59NO15/c1-5-6-9-20(3)32(50-31(44)17-23(34(47)48)15-29(41)42)27(49-30(43)16-22(33(45)46)14-28(39)40)13-19(2)12-24(36)10-7-8-11-25(37)18-26(38)21(4)35/h19-27,32,36-38H,5-18,35H2,1-4H3,(H,39,40)(H,41,42)(H,45,46)(H,47,48)
    Key: UVBUBMSSQKOIBE-UHFFFAOYAH
  • O=C(O)CC(C(=O)O)CC(=O)OC(C(C)CCCC)C(OC(=O)CC(C(=O)O)CC(=O)O)CC(C)CC(O)CCCCC(O)CC(O)C(N)C
Properties
C34H59NO15
Molar mass 721.838 g·mol−1
AppearanceWhite to off-white powder
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Fumonisin B1 is the most prevalent member of a family of toxins, known as fumonisins, produced by multiple species of Fusarium molds, such as Fusarium verticillioides , which occur mainly in maize (corn), wheat and other cereals. Fumonisin B1 contamination of maize has been reported worldwide at mg/kg levels. Human exposure occurs at levels of micrograms to milligrams per day and is greatest in regions where maize products are the dietary staple.

Contents

Fumonisin B1 is hepatotoxic and nephrotoxic in all animal species tested. The earliest histological change to appear in either the liver or kidney of fumonisin-treated animals is increased apoptosis followed by regenerative cell proliferation. While the acute toxicity of fumonisin is low, it is the known cause of two diseases which occur in domestic animals with rapid onset: equine leukoencephalomalacia and porcine pulmonary oedema syndrome. Both of these diseases involve disturbed sphingolipid metabolism and cardiovascular dysfunction.

History

Figure 1: Fusarium ear rot, caused by the fungi Fusarium verticillioides and F. proliferatum, may typically be a more common ear rot of corn. Source: UIUC available at: http://www.extension.umn.edu/cropenews/2007/07MNCN42.html Corn mold.jpg
Figure 1: Fusarium ear rot, caused by the fungi Fusarium verticillioides and F. proliferatum, may typically be a more common ear rot of corn. Source: UIUC available at: http://www.extension.umn.edu/cropenews/2007/07MNCN42.html

In 1970, an outbreak of leukoencephalomalacia in horses in South Africa was associated with the contamination of corn with the fungus Fusarium verticillioides . [1] It is one of the most prevalent seed-borne fungi associated with corn. [2] Another study was done on the possible role of fungal toxins in the etiology of human esophageal cancer in a region in South Africa. The diet of the people living in this area was homegrown corn and F. verticillioides was the most prevalent fungus in the corn consumed by the people with high incidence of esophageal cancer. [2] Further outbreaks of leukoencephalomalacia and people in certain regions with high incidence of esophageal cancer led to more research on F. verticillioides. Soon they found experimentally that F. verticillioides caused leukoencephalomalacia in horses and porcine pulmonary edema in pigs. It was found to be highly hepatotoxic and cardiotoxic in rats. In 1984 it was shown that the fungus was hepatocarcinogenic in rats. [2] The chemical nature of the metabolites causing all this had still not been discovered in 1984. After discovery of the carcinogenicity of the fungus, isolation and chemical characterization of the mycotoxins and carcinogens produced by F. verticillioides was urgent. It wasn't until 1988 that the chemical nature of the carcinogen was unraveled. Fumonisin B1 and fumonisin B2 were isolated from cultures of F. verticillioides at the Programme on Mycotoxins and Experimental Carcinogenesis. [3] The structures were elucidated in collaboration with the Council for Scientific and Industrial Research. [4] Several isomers of fumonisin B1 have been detected in solid rice culture. [5] Now more than 100 different fumonisins are known, the most important ones being fumonisin B1, B2 and B3. [6] [7]

Toxicokinetics

Regarding toxicokinetics there is no human data available, but research on animals has been done.

Absorption

FB1 is taken orally via food. Overall, FB1 is poorly absorbed, less than 6%. [8] Absorption of orally administered fumonisin B1 (10 mg/kg body weight) to rats is low (3.5% of dose) but rapid (Tmax = 1.02 h). [9] FB1 does not significantly permeate through the human skin and hence has no significant systemic health risk after dermal exposure. [10]

Distribution

After absorption, some appears to be retained in liver and kidneys. For rats that were fed diets containing fumonisins for several weeks, the concentrations of the fumonisins in the kidneys were approximately 10-fold higher than in the liver. [11]

Plasma distribution of the absorbed dose conformed to a two-compartment open model and the tissue (liver, kidney) concentration time results were consistent with a one-compartment open model. [9]

Excretion

Elimination half-life in rats is 3.15 h for plasma, 4.07 h for liver, and 7.07 h for kidney. [9] However, FB1 is rapidly excreted mostly in its original form. Small amounts are excreted in urine; the most are excreted in feces. [8]

Toxicodynamics

Because of their similarity, fumonisins are able to inhibit sphingosine-sphinganin-transferases and ceramide synthases and are therefore competitive inhibitors of sphingolipid biosynthesis and metabolism.

Figure 2: Sphingolipid metabolism showing the inhibition of ceramide synthase (x) by fumonisins and the changed concentrations of other compounds caused by this inhibition. Sphingolipid metabolism.png
Figure 2: Sphingolipid metabolism showing the inhibition of ceramide synthase (x) by fumonisins and the changed concentrations of other compounds caused by this inhibition.

Figure 2 shows the sphingolipid metabolism (schematic) and the inhibition caused by fumonisins. Fumonisin B1 inhibits the enzyme ceramide synthase (sphingosine N-acyltransferase), which acylates sphingoid bases. This blocks the formation of ceramide via two pathways. It inhibits de formation via de novo sphinganine and fatty acyl-CoA and via sphingosine produced by the breakdown of ceramide by ceramidase. The inhibition results in increased concentrations of sphinganine, sphingosine and their 1-phosphate metabolites and in decreased concentrations of complex sphingolipids. The accumulation of sphinganine and sphingosine is a primary cause of the toxicity of fumonisin B1 [13] Sphinganine and sphingosine are cytotoxic, and have growth inhibitory effects. Also, these sphingoid bases induce apoptosis. Increased apoptosis seems to play an important role in the toxic effects including tumor induction. [8] However, it should be mentioned that the reduced concentration of ceramide and the increased concentration of sphingosine-1-phosphate (as a result of FB1 intake) cause an inhibition of apoptosis and promote mitosis and regeneration. [13] The balance between the intracellular concentration of compounds that inhibit apoptosis and those that induce apoptosis will determine the cellular response. [14] Also, the decreased concentrations of complex sphingolipids appear to play a role in the abnormal behavior and altered morphology of the affected cells. [11]

Mechanism of action

Figure 3: Proposed mechanism of action of ceramide synthase inhibition by FB1; FB1 mimics regions of the sphingoid base and the fatty acyl-CoA substrates. (Merrill et al., 2001) Ceramidesynthasefb1.png
Figure 3: Proposed mechanism of action of ceramide synthase inhibition by FB1; FB1 mimics regions of the sphingoid base and the fatty acyl-CoA substrates. (Merrill et al., 2001)

The proposed mechanism of action is depicted in figure 3. Fumonisin B1 occupies the space and electrostatic interactions of both sphinganine (or sphingosine) and fatty acyl-CoA in ceramide synthase. The part of FB1 that has structural similarity with sphingoid bases (the aminopentol part) may interact with the sphinganine binding site, whereas the negatively charged tricarbyllic acid groups may interact with the fatty acyl-CoA binding site. [8]

Because FB1 also occupies the fatty acyl-CoA space, it isn't acylated, since acyl-CoA is necessary for the acylation; FB1 only inhibits ceramide synthase. However, when the tricarbillic acid groups are removed from FB1 by hydrolysis, the resulting product (aminopentol, AP1) doesn't only act as an inhibitor, but also as a substrate for ceramide synthase; aminopentol is acylated by ceramide synthase to form N-palmitoyl-AP1. [13] This supports the suggestion that the aminopentol part of FB1 occupies the space of sphinganine in the enzyme. N-palmitoyl-AP1 is an even more potent inhibitor of ceramide synthase and may therefore play a role in the toxicity of nixtamalized fumonisins. [13]

Toxic effects

The risks of fumonisin B1 have been evaluated by The World Health Organization's International Programme on Chemical Safety and the Scientific Committee on Food of the European Commission. They determined a tolerable daily intake for FB1, FB2, FB3, alone or in combination of 2 μg/kg body weight. [15] Until now, nothing about the kinetics and metabolism of fumonisin B1 in humans have been reported. On other animals much research has been done, but it might not be comparable to humans. In mice the elimination of FB1 is very rapid, but in humans it could be much slower considering their body weight. [6] There are several possible pathways that cause toxic effects of Fumonisin B1. Most toxic effects are due to altered sphingolipid metabolism by inhibition of ceramide synthase. Production of reactive oxygen species could occur. This increases oxidative stress and induce lipid peroxidation and could damage cells. In agreement with this some studies showed decreased levels of glutathione in liver, but other studies showed even elevated levels of glutathione. [6] Cytotoxic effects have also been reported. [6] Another effect of exposure to FB1 is apoptosis. This has been observed in a number of different cells and tissues. Inhibition of ceramide synthase is not responsible for this effect. The main factors could be DNA fragmentation and caspase-3 activation. [6] FB1 has also immunotoxic effects, but much more research is necessary to get a clear overview of the effects on the immune system.

Toxic effects in humans

Neural tube defects

Neural tube defect are abnormalities of the brain and spinal cord in the embryo resulting from failure of the neural tube to close. [16] Epidemiological studies and clinical trials have pointed out folate deficiency as a major risk factor for neural tube defects. [17] FB1 disrupts sphingolipid metabolism and therefore this could affect folate uptake and cause neural tube defects. [6] In 1990 and 1991 a sudden outbreak of neural tube defects occurred along the Texas-Mexico border. It is believed that this outbreak might have been due to high levels of FB1 that were observed in corn during previous years. [18] Regions in China and South Africa with high corn consumption also have a high prevalence of neural tube defects. [6] [19]

Esophageal cancer

It is thought that there is a relationship between the occurrence of F. verticillioides and human esophageal cancer. A low socioeconomic status and a less varied diet, that mainly consists of corn and wheat, is associated with the appearance of esophageal cancer. [6] This derives from epidemiologic studies in various countries. Other studies show that higher concentrations of FB1, FB2 and F. verticillioides are present in corn growing in regions with a high percentage of esophageal cancer. This in contrast with regions with low levels of F. verticillioides, FB1 and FB2 in corn. [20] On top of this it seems that people with a high corn intake are at higher risk to develop esophageal cancer than people with low corn intake. This is observed by people in regions in Italy, Iran, Kenia, Zimbabwe, United States and Brazil with high incidence of esophageal cancer. [21] Another study on the relationship between sphingolipid levels and cancer incidence didn't show any significant relationship between serum sphingolipids and risk of esophageal cancer. This is quite remarkable, because elevated levels of sphingolipids sphinganine and sphingosine are believed to be biomarkers for exposure of FB1. [6]

Acute mycotoxicosis

Acute mycotoxicosis is food poisoning by food products contaminated by fungi. In 1995 an outbreak of disease characterized by diarrhea and abdominal pain occurred in 27 villages in India. This was the result of consumption of moldy sorghum and corn due to rain damage. This outbreak was studied and the mycotoxicosis was connected to consumption of unleavened bread. Corn and sorghum samples were collected from the households and examined. The corn and sorghum were contaminated by Fusarium and Aspergillus and contained high levels of FB1 compared with samples of unaffected households. [6]

Toxic effects in animals

Much research has been done on toxic effects of FB1 in animals. In vivo studies indicate that liver and kidneys are the main target organs. [6] Fumonisins are poorly absorbed, rapidly eliminated and not metabolized in animals. [22] In pigs and rats there is a wide distribution of FB1 and small amounts have been found to accumulate only in liver and kidneys. In vervet monkeys, some FB1 is partially hydrolyzed in the gut. [6]

Carcinogenic effects

In rats and mice that were exposed to FB1 tumor formation occurred. Several studies on this subject have been done. Depending on the strain of mice being used different carcinomas were shown. [6] FB1 is shown to be nongenotoxic. Therefore, the mechanisms responsible for cancer development should lie elsewhere. Important mechanisms for cancer development due to fumonisin B1 could be oxidative damage (production of reactive oxygen species) and lipid peroxidation. Hepatic and renal tumors could also be due to apoptosis by FB1. As a response to this there could be continuous regeneration of cells, causing cancer. It seems to be that disrupted sphingolipid metabolism is the causative factor for FB1-induced carcinogenicity, as is the case with the toxic effects. [6] Based on all these animal studies FB1 is classified by The International Agency for Research on Cancer (IARC) as possibly carcinogenic to humans (Group 2B). [23]

Porcine pulmonary edema

Porcine pulmonary edema due to FB1 is intensively studied after the first report in 1981 of swine with pulmonary edema after exposure to corn contaminated with F. verticillioides. Alteration in sphingolipid biosynthesis are reported, especially in lung, heart, kidney and liver tissue. Lethal pulmonary edema was developed within 4–7 days after exposure to feed with concentrations of FB1 >16 mg/kg body weight (>92 parts per million). Doses of 10 parts per million caused a milder form of pulmonary edema. [6]

Equine leukoencephalomalacia

Leukoencephalomalacia is a neurotoxic disease of horses. Outbreaks of this disease in the 20th century resulted in a number of studies. Apparently FB1 was the cause for this disease. There were shown elevated levels of serum enzyme levels that indicate liver damage. They were normally observed by an elevation of the sphinganine/sphingosine ratio. FB1 possibly induces cardiovascular function, because of the elevated sphinganine/sphingosine ratio. This could be one of the main factors that causes leukoencephalomalacia. [24]

Toxicity in laboratory animals

Effects of feeding rats with FB1 for up to 90 days were usually nephrotoxicity. Between different strains of rats, sensitivity to FB1 varied. In the kidneys the main effect was apoptosis. Also tubular atrophy and regeneration as well as decreased kidney weight was reported. [6] Histopathologic effects on rat liver were reported after both short- and long-term exposure. The main cause was apoptosis. Mice don't seem to be very sensitive to nephrotoxic effects in comparison with rats. In mouse kidneys little histological changes were seen by high dose exposure. The liver was also the main target organ in mice. Pathology is similar as in rats, with apoptosis and hepatocellular hyperplasia. [6] Fumonisin B1 is possibly embryotoxic if the dose is maternally toxic. A number of studies on genotoxicity indicated no mutagenetic effects. Although fumonisin could damage DNA directly by production of reactive oxygen species. [6] Mouse embryos were exposed to FB1 and they showed inhibited sphingolipid synthesis and growth. It caused neural tube defects. Folic acid uptake was dramatically inhibited. Treatment after exposure with folic acid reduced neural tube defects by 50–65%. [6]

Tolerable daily intake

The risks of fumonisin B1 have been evaluated by The World Health Organization's International Programme on Chemical Safety and the Scientific Committee on Food of the European Commission. They determined a tolerable daily intake for FB1, FB2, FB3, alone or in combination of 2 μg/kg body weight. [15]

Detoxification

The inhibition of ceramide synthase by FB1 is thought to be reversible, since the binding is formed by noncovalent interactions. Factors that will probably induce this reversibility are reduction of cellular FB1-concentration and increasing of cellular concentrations of the substrates for ceramide synthase. [13] Also, the rate of removal of the accumulated sphinganine and sphingosine will affect the detoxification. The information on metabolism and biotransformation of FB1 is very sparse. However, metabolism most likely occurs in the gut since partially hydrolysed and fully hydrolysed FB1 were recovered in faeces but not in bile of vervet monkeys. [8] Bioavailability of FB1 can be reduced by treating fumonisin-contaminated corn with glucomannans extracted from the cell wall of the yeast Saccharomyces cerevisiae. These polysaccharides are able to bind certain mycotoxins and have a 67% binding capacity for fumonisins. [25]

Related Research Articles

<span class="mw-page-title-main">Sphingolipid</span> Family of chemical compounds

Sphingolipids are a class of lipids containing a backbone of sphingoid bases, which are a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named after the mythological sphinx because of their enigmatic nature. These compounds play important roles in signal transduction and cell recognition. Sphingolipidoses, or disorders of sphingolipid metabolism, have particular impact on neural tissue. A sphingolipid with a terminal hydroxyl group is a ceramide. Other common groups bonded to the terminal oxygen atom include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids.

<span class="mw-page-title-main">Sphingomyelin</span> Class of chemical compounds

Sphingomyelin is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphocholine and ceramide, or a phosphoethanolamine head group; therefore, sphingomyelins can also be classified as sphingophospholipids. In humans, SPH represents ~85% of all sphingolipids, and typically make up 10–20 mol % of plasma membrane lipids.

<span class="mw-page-title-main">T-2 mycotoxin</span> Chemical compound

T-2 mycotoxin is a trichothecene mycotoxin. It is a naturally occurring mold byproduct of Fusarium spp. fungus which is toxic to humans and other animals. The clinical condition it causes is alimentary toxic aleukia and a host of symptoms related to organs as diverse as the skin, airway, and stomach. Ingestion may come from consumption of moldy whole grains. T-2 can be absorbed through human skin. Although no significant systemic effects are expected after dermal contact in normal agricultural or residential environments, local skin effects can not be excluded. Hence, skin contact with T-2 should be limited.

<span class="mw-page-title-main">Ceramide</span> Family of waxy lipid molecules

Ceramides are a family of waxy lipid molecules. A ceramide is composed of sphingosine and a fatty acid joined by an amide bond. Ceramides are found in high concentrations within the cell membrane of eukaryotic cells, since they are component lipids that make up sphingomyelin, one of the major lipids in the lipid bilayer. Contrary to previous assumptions that ceramides and other sphingolipids found in cell membrane were purely supporting structural elements, ceramide can participate in a variety of cellular signaling: examples include regulating differentiation, proliferation, and programmed cell death (PCD) of cells.

<span class="mw-page-title-main">Citrinin</span> Chemical compound

Citrinin is a mycotoxin which is often found in food. It is a secondary metabolite produced by fungi that contaminates long-stored food and it can cause a variety of toxic effects, including kidney, liver and cell damage. Citrinin is mainly found in stored grains, but sometimes also in fruits and other plant products.

<span class="mw-page-title-main">Fumonisin B2</span> Chemical compound

Fumonisin B2 is a fumonisin mycotoxin produced by the fungi Fusarium verticillioides and Aspergillus niger.

<span class="mw-page-title-main">Lipid signaling</span> Biological signaling using lipid molecules

Lipid signaling, broadly defined, refers to any biological cell signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses. Lipid signaling is thought to be qualitatively different from other classical signaling paradigms because lipids can freely diffuse through membranes. One consequence of this is that lipid messengers cannot be stored in vesicles prior to release and so are often biosynthesized "on demand" at their intended site of action. As such, many lipid signaling molecules cannot circulate freely in solution but, rather, exist bound to special carrier proteins in serum.

<span class="mw-page-title-main">Fumonisin</span> Group of chemical compounds

The fumonisins are a group of mycotoxins derived from Fusarium and their Liseola section. They have strong structural similarity to sphinganine, the backbone precursor of sphingolipids.

Sphingosine-1-phosphate (S1P) is a signaling sphingolipid, also known as lysosphingolipid. It is also referred to as a bioactive lipid mediator. Sphingolipids at large form a class of lipids characterized by a particular aliphatic aminoalcohol, which is sphingosine.

Mycotoxicology is the branch of mycology that focuses on analyzing and studying the toxins produced by fungi, known as mycotoxins. In the food industry it is important to adopt measures that keep mycotoxin levels as low as practicable, especially those that are heat-stable. These chemical compounds are the result of secondary metabolism initiated in response to specific developmental or environmental signals. This includes biological stress from the environment, such as lower nutrients or competition for those available. Under this secondary path the fungus produces a wide array of compounds in order to gain some level of advantage, such as incrementing the efficiency of metabolic processes to gain more energy from less food, or attacking other microorganisms and being able to use their remains as a food source.

<span class="mw-page-title-main">Sterigmatocystin</span> Chemical compound

Sterigmatocystin is a polyketide mycotoxin produced by certain species of Aspergillus. The toxin is naturally found in some cheeses.

In enzymology, sphingosine N-acyltransferases (ceramide synthases (CerS), EC 2.3.1.24) are enzymes that catalyze the chemical reaction of synthesis of ceramide:

<span class="mw-page-title-main">Ceramide synthase 1</span> Protein-coding gene in the species Homo sapiens

Ceramide synthase 1 also known as LAG1 longevity assurance homolog 1 is an enzyme that in humans is encoded by the CERS1 gene.

<span class="mw-page-title-main">Ceramide synthase 2</span> Protein-coding gene in the species Homo sapiens

Ceramide synthase 2, also known as LAG1 longevity assurance homolog 2 or Tumor metastasis-suppressor gene 1 protein is an enzyme that in humans is encoded by the CERS2 gene.

Ceramide synthase 4 (CerS4) is an enzyme that in humans is encoded by the CERS4 gene and is one of the least studied of the ceramide synthases.

Ceramide synthase 5 (CerS5) is the enzyme encoded in humans by the CERS5 gene.

<span class="mw-page-title-main">Nivalenol</span> Type of mycotoxin

Nivalenol (NIV) is a mycotoxin of the trichothecene group. In nature it is mainly found in fungi of the Fusarium species. The Fusarium species belongs to the most prevalent mycotoxin producing fungi in the temperate regions of the northern hemisphere, therefore making them a considerable risk for the food crop production industry.

The 1-deoxysphingolipids (1-deoxySLs) are an atypical and recently discovered class of sphingolipids (SLs). They are formed during the nove synthesis pathway and their essential C1-OH deficit causes the malfunctions of the following transformations to achieve complex sphingolipids. In general, sphingolipids are formed during a reaction that is catalyzed by the SPT enzyme (serine-palmitoyltransferase) where the condensation of serine and palmitoyl-CoA takes place. The origin of this rare sphingolipid, though, is due to a defect of the SPT which can also use alanine or glycine. This change is what forms the 1-deoxySL.

<span class="mw-page-title-main">PR toxin</span> Chemical compound

Penicillin Roquefort toxin is a mycotoxin produced by the fungus Penicillium roqueforti. In 1973, PR toxin was first partially characterized by isolating moldy corn on which the fungi had grown. Although its lethal dose was determined shortly after the isolation of the chemical, details of its toxic effects were not fully clarified until 1982 in a study with mice, rats, anesthetized cats and preparations of isolated rat auricles.

<span class="mw-page-title-main">Fumonisin B4</span> Chemical compound

Fumonisin B4 is a fumonisin mycotoxin produced mainly by the fungi Fusarium proliferatum, Fusarium verticillioides. Recently FB4 has been detected in fungi Aspergillus niger and in several Tolypocladium species.

References

  1. ↑ Marasas WF, Nelson PE, Toussoun TA (1984). Toxigenic Fusarium Species. Identity and Mycotoxicology. Pennsylvania State University Press.
  2. 1 2 3 Marasas WF. (May 2001). "Discovery and occurrence of the fumonisins: A historical perspective". Environ Health Perspect. 109 suppl 2 (Suppl 2): 239–43. doi:10.1289/ehp.01109s2239. PMC   1240671 . PMID   11359691.
  3. ↑ Gelderblom WC, Jasklewicz K, Marasas WF, Thiel PG, Horak MJ, Vleggaar R, Kriek NP (1988). "Fumonisins – novel mycotoxins with cancer promoting activity produced by Fusarium moniliforme". Appl Environ Microbiol. 54 (7): 1806–1811. Bibcode:1988ApEnM..54.1806G. doi:10.1128/aem.54.7.1806-1811.1988. PMC   202749 . PMID   2901247.
  4. ↑ Bezuidenhout SC, Gelderblom WC, Gorst-Allman CP, Horak RM, Marasas WF, Spiteller G, Vleggaar R (1988). "Structure eludicidation of the fumonisins, mycotoxins from Fusarium moniliforme". J Chem Soc Chem Commun (11): 743–745. doi:10.1039/c39880000743.
  5. ↑ Tibor Bartok; Laszlo Tolgyesi; Andras Szekeres; Monika Varga; Richard Bartha; Arpad Szecsi; Mihaly Bartok; Akos Mesterhazy (2010). "Detection and characterization of twenty-eight isomers of fumonisin B1 (FB1) mycotoxin in a solid rice culture infected with Fusarium verticillioides by reversed-phase high-performance liquid chromatography/electrospray ionization time-of-flight and ion trap mass spectrometry". Rapid Communications in Mass Spectrometry. 24 (1): 35–42. Bibcode:2010RCMS...24...35B. doi:10.1002/rcm.4353. PMID   19960490.
  6. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 H Stockmann-Juvalla; K Savolainen (2008). "A review of the toxic effects and mechanisms of action of fumonisin B1". Human & Experimental Toxicology. 27 (11): 799–809. Bibcode:2008HETox..27..799S. doi: 10.1177/0960327108099525 . PMID   19244287. S2CID   8722428.
  7. ↑ Tibor Bartok; Arpad Szecsi; Andras Szekeres; Akos Mesterhazy; Mihaly Bartok (2006). "Detection of new fumonisin mycotoxins and fumonisin-like compounds by reversed-phase high-performance liquid chromatography/electrospray ionization ion trap mass spectrometry". Rapid Communications in Mass Spectrometry. 20 (16): 2447–62. Bibcode:2006RCMS...20.2447B. doi:10.1002/rcm.2607. PMID   16871522.
  8. 1 2 3 4 5 European commission (2000). "Fumonisin B1". Opinion of the Scientific Committee on Food on Fusarium Toxins (27).
  9. 1 2 3 MR Martinez-Larranaga (December 1999). "Toxicokinetics and oral bioavailability of fumonisin B1". Veterinary and Human Toxicology. 41 (6): 357–62. PMID   10592940.
  10. ↑ Boonen, Jente; Malysheva, Svetlana V.; Taevernier, Lien; Diana Di Mavungu, José; De Saeger, Sarah; De Spiegeleer, Bart (2012). "Human skin penetration of selected model mycotoxins". Toxicology. 301 (1–3): 21–32. Bibcode:2012Toxgy.301...21B. doi:10.1016/j.tox.2012.06.012. PMID   22749975.
  11. 1 2 Riley, R.T.; Voss, K.A. (2006). "Differential sensitivity of rat kidney and liver to fumonisin toxicity: organ-specific differences in toxin accumulation and sphingoid base metabolism". Toxicol. Sci. 92 (1): 335–345. CiteSeerX   10.1.1.510.3075 . doi: 10.1093/toxsci/kfj198 . PMID   16613836.
  12. ↑ Voss et al., 2007[ full citation needed ]
  13. 1 2 3 4 5 Merrill Jr.; A.H.; Sullards, M.C.; Wang, E.; Voss, K.A.; Riley, R.T. (2001). "Sphingolipid metabolism: roles in signal transduction and disruption by fumonisins". Environmental Health Perspectives. 109 (Suppl 2): 283–289. doi:10.2307/3435020. JSTOR   3435020. PMC   1240677 . PMID   11359697.
  14. ↑ Riley RT, Enongen E, Voss KA, Norred WP, Meredith FI, Sharma RP, Williams D, Merrill AH (2001). "Sphingolipid perturbations as mechanisms for fumonisin carcinogenesis". Environmental Health Perspectives. 109 (Suppl 2): 301–308. doi:10.2307/3435022. JSTOR   3435022. PMC   1240679 . PMID   11359699.
  15. 1 2 SCF. "Updated opinion of the Scientific Committee on Food on Fumonisin B1,B2 and B3" (PDF). Retrieved April 1, 2011.{{cite journal}}: Cite journal requires |journal= (help)
  16. ↑ "Neural Tube Defects (NTD)". Archived from the original on 2011-03-04. Retrieved April 1, 2011.
  17. ↑ Blom HJ, Shaw GM, den Heijer M, Finnel RH (2006). "Neural tube defects and folate: case far from closed". Nat Rev Neurosci. 7 (9): 724–731. doi:10.1038/nrn1986. PMC   2970514 . PMID   16924261.
  18. ↑ "Neural Tube Defects and the Texas-Mexico Border". Archived from the original on February 20, 2011. Retrieved April 1, 2011.
  19. ↑ Cornell J, Nelson MM, Beighton P (1975–1980). "Neural tube defects in Cape Town area". South African Medical Journal. 64 (3): 83–84. PMID   6346521.
  20. ↑ Wild CP, Gong YY (29 October 2009). "Mycotoxins and human disease: a largely ignored global health issue". Carcinogenesis. 31 (1): 71–82. doi:10.1093/carcin/bgp264. PMC   2802673 . PMID   19875698.
  21. ↑ International programme on chemical safety (2001). "WHO. Safety evaluation of certain mycotoxins in food (WHO food additives series 47)". Geneva: World Health Organization: 103–279.{{cite journal}}: Cite journal requires |journal= (help)
  22. ↑ International programme on chemical safety (2000). "WHO. Fumonisin B1 (Environmental health criteria 219)". Geneva: World Health Organization.{{cite journal}}: Cite journal requires |journal= (help)
  23. ↑ International Agency for Research on Cancer (IARC) (2002). "Summaries & Evaluations, Fumonisin B1" (82): 301.{{cite journal}}: Cite journal requires |journal= (help)
  24. ↑ Goel S; Schumacher J; Lenz SD; Kemppainen BW (1996). "Effects of fusarium moniliforme isolates on tissue and serum sphingolipid concentrations in horses". Vet Hum Toxicol. 38 (4): 265–70. PMID   8829343.
  25. ↑ Yiannikouris A.; Jouany J. (2002). "Mycotoxins in feeds and their fate in animals: a review". Animal Research. 51 (2): 81–99. doi: 10.1051/animres:2002012 .
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