In the kidney cells of monkeys, fumonisin B1 alters gene expression and signal transduction pathways [3]. In LLC-PK1 renal cells, fumonisin B1 enhances the first breakdown of sphingolipid metabolism and the build-up of sphingosine, leading to apoptotic DNA damage in rat astrocytes [3].
Fumonisin B1 (FB1) is a well-known liver and kidney carcinogen in rodents and humans. The aim of the present study was to investigate the effect of FB1 on the proliferation and cell cycle of the normal human liver cell line HL-7702 and to explore the underlying molecular mechanisms of action. The cells were treated with FB1 (0.0, 0.1, 1.0, 10.0 and 100.0 µmol/l) for 24, 48, 72 and 96 h. Cell proliferation was assessed by colorimetric assay. Cell cycle analysis was performed by flow cytometry. The mRNA and protein expression of cyclin E and P21 were determined by RT‑PCR and western blot analysis, respectively. FB1 was initially demonstrated to significantly inhibit the proliferation of HL-7702 cells; however, cell proliferation increased with increasing treatment time. The percentage of cells in the G0/G1 phase was significantly increased by FB1; however, significantly decreased with an increasing concentration of FB1. The mRNA expression of cyclin E was upregulated and then gradually downregulated with increasing treatment time. The mRNA expression of P21 was significantly increased following treatment with 0.1 µmol/l FB1, and decreased following treatment with 10.0 and 100.0 µmol/l FB1 for different treatment durations. Western blot analysis showed that FB1 significantly increased the protein expression of cyclin E and significantly decreased the protein expression of P21 at various concentrations and treatment durations. Our results demonstrated that FB1 affects the cell cycle of normal human liver cells and that the underlying mechanism of action is associated with alterations in the expression levels of cyclin E and P21 induced by FB1[3].

Adult male C57BL/6 mice were injected with FB1 (fumonisin B1) (8 mg/kg, i.p.) or its vehicle and 30 min thereafter received with a low dose of the classical convulsant pentylenetetrazol (PTZ, 30 mg/kg, i.p.) or its vehicle. After behavioral evaluation the cerebral cortex and the hippocampus were collected for analysis of Na(+),K(+)-ATPase activity, mitochondrial membrane potential (ΔΨm) and mitochondrial complex I and II activities. FB1 reduced the latency for PTZ-induced myoclonic jerks and increased the number of these events. Altogether, present results indicate that FB1 causes brain hyperexcitability in vivo, and that mitochondrial dysfunction may represent a potential underlying mechanism.

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Three recently described and toxicologically important mycotoxins, fumonisin B1 (FB1), fumonisin B2 (FB2), and fumonisin B3 (FB3), produced by Fusarium moniliforme in various grains, have been associated with a number of diseases in both humans and animals. The toxicity of purified FB1, FB2, and FB3, individually and in combination (3:1:1 ratio), were evaluated with regard to their embryo toxicity by injection of the toxins into the air cell of chicken eggs at 72 h of incubation. Under these conditions, FB1 at doses of 0, 2, 4, 8, 16, 32, and 64 microg per egg resulted in embryonic mortality of 5, 12.5, 17.5, 20.0, 52.5, 77.5, and 100%, respectively. The 50% lethal dose for FB1, when injected into the air cell of embryonating chicken eggs, was determined to be 18.73 microg per egg. A comparison of the toxicity of FB1, FB2, and FB3, individually and in combination (3:1:1 ratio), at doses of 16 microg of total fumonisin per egg, indicated that the toxicity of the fumonisins differed, FB1 being the most toxic. Microscopic examination of chicken embryos exposed to fumonisin did not reveal any gross developmental abnormalities; however, severe hemorrhages of the head, neck, and thoracic area of the dead embryos were evident.[1]

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The fumonisin mycotoxins are produced by Fusarium moniliforme Sheldon, a contaminant of corn worldwide. The two most abundant analogues (fumonisins B1 and B2) are known to be potent inhibitors of sphingosine N-acyltransferase (ceramide synthase) and hence to disrupt de novo sphingolipid biosynthesis. The sphingoid bases, sphingosine and sphinganine (and hence their ratio), were measured at varying intervals over a period of 60 weeks in the serum of non-human primates (vervet monkeys; Cercopithecus aethiops) which were consuming diets containing 'low' and 'high' amounts of F. moniliforme culture material, such that their total daily fumonisin intake was approximately 0.3 and 0.8 mg/kg body weight/day, respectively. Although no significant differences were found in the serum levels of sphingosine compared to controls, serum sphinganine levels in the experimental groups (mean of 219 nM and 325 nM, respectively) were significantly (P = 0.02) elevated above the levels in controls (mean 46 nM). As a consequence, the ratio sphinganine:sphingosine was significantly (P = 0.003) elevated from a mean of 0.43 in the control group to 1.72 and 2.57 in the experimental groups, respectively. Similar changes in sphingolipid profiles were also measured in urine with an increase of the ratio from 0.87 in controls to 1.58 and 2.17 in the experimental groups, although the differences were not statistically significant. Hence, the disruption of sphingolipid biosynthesis in vervet monkeys by fumonisins in culture material added to their diet can effectively be monitored in the serum as an elevation of the sphinganine:sphingosine ratio [2].

Cell viability assay [3]
HL-7702 cells (1×104 cells/100 μl/well) were seeded in 96-well plates with 100 μl culture medium containing 5% FBS, and incubated for 24 h to allow cells to attach to the bottom of the plate. The cells were incubated with Fumonisin B1 (FB1) (0.0, 0.1, 1.0, 10.0 and 100.0 μmol/l) for 24, 48, 72 and 96 h. After 100 μl MTT (5 mg/ml in PBS) was added in the culture medium, the cells were incubated for 4 h at 37°C in a humidified atmosphere with 5% CO2. The medium was aspirated and the cells were suspended in 150 μl DMSO. The absorption was measured at 490 nm with a Mithras LB 940 Multimode Microplate reader. The inhibition rate of cell proliferation was calculated as follows: 1- [optical density (OD) of the experimental samples/OD of the control] × 100%. The experiment and assay were repeated at least three times.

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Cell harvesting [3]
HL-7702 cells in a logarithmic growth phase were plated at a density of 105 cells/ml in 50-cm2 culture flasks and allowed to grow in 4 ml culture medium. Following cell attachment, the culture medium was discarded. The cells were then treated with Fumonisin B1 (FB1) (0.0, 0.1, 1.0, 10.0 and 100.0 μmol/l) for 24, 48, 72 and 96 h. Then, the cells were trypsinized and collected for cell cycle analysis, or washed twice with ice-cold PBS and removed from the surface of the flask by using a rubber scraper for RT-PCR and western blot analysis.

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Cell cycle analysis [3]
The cell cycle phase was examined using a Becton-Dickinson FACSCalibur flow cytometer. The cells were stained with Vindelov's reagent (40 mmol/l Tris, pH 7.6; 100 mmol/l NaCl; 10 mg/ml RNase A; 7.5% PI and 0.1% Nonidet P-40), and data from 10,000 cells were collected for each data file. The experiment and assay were repeated three times.

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Semiquantitative RT-PCR [3]
Semiquantitative RT-PCR was used to assess the mRNA expression of cyclin E and P21. Briefly, after the HL-7702 cells were treated with Fumonisin B1 (FB1) , total RNA was extracted using TRIzol, followed by chloroform re-extraction and isopropanol precipitation. Purified RNA was dissolved in RNase-free water and quantitated by spectrophotometry. Reverse transcription was performed using the RevertAid First Stand cDNA Synthesis kit with oligo(dT) priming under standard conditions suggested by the supplier. PCR was performed in a 50-μl reaction containing PCR mix SYBR-Green, each primer and cDNA. PCR was performed under the following conditions: 94°C for 2 min for initial denaturation, followed by 28 cycles of 94°C for 1 min, 55°C for 1 min and 72°C for 2 min. The primer sequences used were: 5′-ATACAGACCCACAGAGACAG-3′ and 5′-TGCCATCCACAGAAATACTT-3′ for cyclin E; 5′-CAGGGGACAGCAGAGGAAGA-3′ and 5′-GGGCGGCCAGGGTATGTAC-3′ for P21 and 5′-ACGGATTTGGTCGTATTG-3′ and 5′-TGATCTTGAGGCTGTTGTC-3′ for GAPDH. The size of the predicted product was visualized by 1.7% agarose gel electrophoresis with EB staining under ultraviolet (UV) illumination. The amounts of PCR products were determined by densitometry analysis using the GelDoc-It™ imaging system. Semiquantitative PCR results were generated by grading a ratio between the densitometry results of the target cytokines and GAPDH.

Experiment 1 was a dose-ranging experiment utilizing only Fumonisin B1 (FB1) . A total of 360 eggs was divided randomly into nine groups of 40 eggs each. To properly control the experiments, three control groups were used. The first control group consisted of eggs that were incubated as they were received from the hatching egg source (control). The second control group consisted of eggs that were drilled, the membrane was pierced with the injecting nee- dle, no solution was injected, and then the eggs were sealed with glue (drilled). In the third control group, eggs were drilled, and 10 μL of methanol:water (1:1 vol:vol) was injected as described previously and then sealed im- mediately with glue (solvent). Six additional groups of 40 eggs each were injected with FB 1 at a dose of 2, 4, 8, 16, 32, or 64, μg of FB1 per egg, respectively. Immediately after injection, all eggs were returned to the incubator and assessed for viability at 7, 10, 14, and 18 d of incubation by candling each egg. Eggs containing a dead embryo were opened, the embryo was weighed, and a visual inspection of the embryo was made. All eggs with a viable embryo FIGURE 3. The cumulative mortality of chicken embryos in response to graded doses of fumonisin B 1 (FB1) (Experiment 1). on Day 18 were opened and visually assessed, and final mortality was calculated. [1]

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Experiments 2 and 3 were designed to compare the toxicity of Fumonisin B1 (FB1) , FB 2, and FB 3. In Experiment 2, a total of 350 eggs containing viable embryos, determined by candling each egg after 72 h of incubation, were divided into seven groups of 50 eggs each. Three control groups, as described in Experiment 1, were also used. The treat- ments were FB 1, FB 2, and FB 3, individually, and a combi- nation of FB 1, FB 2, and FB 3, in a 3:1:1 ratio, respectively. In Experiment 2, each test solution was injected such that each egg received 2 μg of total fumonisin. Mortality was determined by candling on 7, 10, 14, and 18 d of incuba- tion. Eggs with dead embryos at each candling time were opened and visually inspected for the presence of gross abnormalities. Viable embryos were returned to the incu- bator on Day 18, and the wet bulb temperature was ad-justed to 32.2 C. Hatchability was determined on Day 22 of incubation. All chicks that hatched were weighed on Day 22. [1]

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The six female vervet monkeys monitored during this study were the subjects of an ongoing long-term study on the pathological effects of ingestion of F. moniliforme MRC 826 culture material at levels I 1% of a low-fat carbohydrate diet. The treatment of the monkeys and the composition of their diet have previously been described (Fincham er al., 1992). At the start of this current study (referred to as week 0), the monkeys were, on average, 120 months old and had already been subject to treatment for a period of 106 months. The composition of the diet remained unchanged over the time of the current study. The six monkeys were the surviving members of the original three groups composing the long-term dietary study. The control group (individuals #707 and #708) received diets similar to the experimental group but with control corn in place of F. moniliformr culture material added to the diet. Individuals #7lO and #7l I received a ‘low’-dose contaminated diet (with 0.5% culture material resulting in an exposure of approximately 0.3 mg total fumonisins/kg body weight/day) and individuals #709 and #712 received a ‘high’-dose contaminated diet (with 1% culture material resulting in an exposure of approximately 0.8 mg total fumonisins (such as Fumonisin B1 (FB1) )/kg body weight/day). In each case the added material represents a minimal addition to the diet.[2]

Absorption, Distribution and Excretion
Fumonisin B1 (FB1), the major compound in the fumonisin group of secondary metabolites of Fusarium moniliforme Sheldon, is associated with some human and animal diseases. After intraperitoneal dosing to rats (7.5 mg/kg), FB1 was rapidly absorbed and reached a maximum concentration in plasma within 20 min after injection. Thereafter, it underwent rapid removal from plasma, displaying a mono-exponential elimination phase that fitted a one-compartment model with a half-life of 18 min. Collection of 24- and 48-hr urine samples indicated that only 16% of the applied dose was eliminated unmetabolized in urine, all within the first 24-hr period following dosing. In contrast to this, a similar dose of FB1 given by gavage resulted in the recovery of only 0.4% of the FB1 in urine.
Fumonisin B1 (FB1), a toxic and carcinogenic secondary metabolite of the fungus Fusarium moniliforme Sheldon, was administered either by i.v. injection or by gavage to vervet monkeys (Cercopithecus aethiops). FB1 dosed by i.v. injection to two female vervet monkeys was rapidly eliminated from plasma with a mean half-life during the elimination phase of 40 min. Analysis of urine and faeces over a 5 day period after dosing gave an average 47% recovery of the dose as FB1 and its hydrolysed analogues. Two female vervet monkeys were given a single gavage dose of 14C-labelled FB1. During the subsequent 3 day period, faecal excretion of radioactivity accounted for an average of 61% of the administered dose and urinary excretion 1.2%. Residual radioactivity was recovered in low levels from skeletal muscle (1%), liver (0.4%), brain (0.2%), kidney, heart, plasma, red blood cells and bile (each 0.1%), while the contents of the intestines accounted for a further 12% of the radioactive dose. In total, 76% of the administered radioactivity was recovered. Analysis of the faeces, intestinal contents and urine indicated that over 90% of the radioactivity in these samples was due to FB1 and its hydrolysis products.
A method has been developed for the determination of fumonisin B1 (FB1) in the feces of non-human primates (vervet monkeys). The animals were dosed with 14C-labelled FB1, and the radioactive compounds in faeces were recovered by repeated extractions with 0.1 M ethylenediaminetetraacetic acid. The extracts were cleaned-up on a reversed-phase (C18) solid-phase extraction cartridge, and FB1 was determined by o-phthaldialdehyde derivatization and reversed-phase HPLC. The analytical method for the determination of FB1 in the fecal extracts was reproducible [2.6% relative standard deviation (RSD)] and accurate (recovery from spiked blank extracts of 93 +/- 2.9% RSD). Confirmation of the identification of FB1 in faeces was achieved using HPLC and thin-layer chromatography, which showed that the radioactivity extracted corresponded mainly to FB1 and a new metabolite with chromatographic properties similar to those of the mycotoxin. The new metabolite was identified by mass spectrometry and nuclear magnetic resonance spectroscopy to be an equilibrium mixture of the two structural isomers of partially hydrolysed FB1, which are formed by hydrolysis of one of the ester groups of the mycotoxin.
The mycotoxin fumonisin B1 (FB1) causes a variety of health problems in animals, while epidemiological evidence suggests it is linked to human esophageal cancer. We investigated the carry-over of FB1 into bovine milk using the isolated perfused bovine udder. Two mg of FB1 was injected into the perfusion blood of 3 udders, and milk and perfused serum levels were determined for 150 min. FB1 passed through the mammary barrier into the milk, but in such low concentrations as to present a negligible risk for consumers.

Toxicity Summary
IDENTIFICATION: Fumonisin B1 is the most prevalent of the fumonisins and produced by the fungus Fusarium moniliforme and other F. species. The pure substance is a white hygroscopic powder and is soluble in water, acetonitrile-water and methanol. The material is stable at food processing temperatures and light. Fumonisin B1 is the most common fungal metabolite associated with maize. Significant accumulation in maize occurs when weather conditions favor kernel rot. HUMAN EXPOSURE: There are no confirmed records of acute toxicity associated with this compound. Available correlation studies suggest a link between dietary exposure and esophageal cancer. Other studies are inconclusive as to the potential carcinogenicity of Fumonisin B1. ANIMAL/PLANT STUDIES: Fumonisin B1 is hepatotoxic in all animal species tested including mice, rats, equids, pigs, rabbits and non-human primates. With the exception of Syrian hamsters, embryotoxicity or teratogenicity is only observed concurrent with or subsequent to maternal toxicity. Fumonisins are nephrotoxic in pigs, rats, sheep, mice and rabbits. In rats and rabbits, renal toxicity occurs at lower doses than hepatotoxicity. The fumonisins are known to cause equine leukoencephalomalacia and porcine pulmonary edema syndrome. It is hepatocarcinogenic to male rats in one strain and nephrocarcinogenic in another strain. Fumonisin B1 is a specific inhibitor of de novo sphingolipid metabolism. This compound inhibits cell growth and causes accumulation of free sphingoid bases and alteration of lipid metabolism in animals, plants and in some yeasts such as Saccharomyces cerevisae. It did not induce gene mutations in bacteria or unscheduled DNA synthesis in primary rat hepatocytes, but induced a dose dependent increase in chromosomal aberrations at low concentrations. This compound is phytotoxic, damages cell membranes and reduces chlorophyll synthesis. This compound is poorly absorbed when dosed orally based on studies using pigs, laying hens and Vervet monkeys and it is rapidly eliminated from the plasma or circulation and recovered in the feces; biliary excretion is important; enterohepatic cycling is important in some animals. Small amounts are excreted in the urine, and some is retained in the liver and kidney.

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The Committee reviewed the studies that have become available since the previous evaluation in 2011, and concluded that they would not change the overall toxicological assessment performed previously by the Committee. Thus, the previously established group PMTDI of 2 µg/kg bw for FB1, FB2 and FB3, alone or in combination, was retained by the current Committee. The Committee noted that the international exposure estimates for FB1 and total fumonisins were lower than those estimated by the Committee at its seventy-fourth meeting in 2011. In the current assessment, a larger part of the occurrence data was from countries belonging to the WHO European Region compared with 2011, resulting in lower overall fumonisin levels in maize. In the current assessment, no information on fumonisin levels in maize was available from countries belonging to the African, Eastern Mediterranean or South-East Asia regions, where higher fumonisin concentrations are typically detected. Given these limitations of the occurrence data used in the exposure assessment and high exposures reported in the literature in some countries, it is likely that the exposures to fumonisins in areas where maize is a staple food and high contamination with fumonisins can occur are higher than those estimated by the Committee at this meeting, as can be seen in the previous evaluation, which was based on a larger and more representative data set. At the eighty-third meeting the Committee also evaluated co-exposure to aflatoxins and fumonisins. Fumonisins and aflatoxins are both frequent contaminants in cereals and cerealbased foods. Aflatoxins are common contaminants in groundnuts and tree nuts. Co-exposure to both mycotoxins is likely in areas where these foods are regularly consumed. Although evidence in laboratory animals from the previous and the present evaluations has suggested an additive or synergistic effect of fumonisin and aflatoxin co-exposure in the development of preneoplastic lesions or hepatocellular carcinoma, currently no data are available on such effects in humans. The Committee concluded that there are few data available to support co-exposure as a contributing factor in human disease. However, the interaction between AFB1, a compound with known genotoxic properties, and fumonisins, which have the potential to induce regenerative cell proliferation (particularly at exposures above the PMTDI), remains a concern. This is due to the fact that the incidences of chronic liver disease and stunting are high in the areas of the world where the exposures to both mycotoxins are high and the co-exposure has been confirmed with biomarkers.

[1]. The toxicity of fumonisin B1, B2, and B3, individually and in combination, in chicken embryos. Poult Sci. 2001 Apr;80(4):401-7.

[2]. Disruption of sphingolipid metabolism in non-human primates consuming diets of fumonisin-containing Fusarium moniliforme culture material. Toxicon. 1996 May;34(5):527-34.

[3]. Effect of fumonisin B₁ on the cell cycle of normal human liver cells. Mol Med Rep. 2013 Jun;7(6):1970-6.

Fumonisin B1 can cause cancer according to The World Health Organization's International Agency for Research on Cancer (IARC) and The National Toxicology Program.
Fumonisin B1 is a diester that results from the condensation of the 1-carboxy groups of two molecules of propane-1,2,3-tricarboxylic acid with hydroxy groups at positions 14 and 15 of (2S,3S,5R,10R,12S,14S,15R,16R)-2-amino-12,16-dimethylicosane-3,5,10,14,15-pentol. It has a role as a metabolite and a carcinogenic agent. It is a fumonisin, a primary amino compound, a diester and a triol. It is functionally related to a (2S,3S,5R,10R,12S,14S,15R,16R)-2-amino-12,16-dimethylicosane-3,5,10,14,15-pentol. It is a conjugate acid of a fumonisin B1(3-).
Macrofusine has been reported in Streptomyces and Arabidopsis thaliana with data available.
Fumonisin B1 is a mycotoxin produced by Fusarium moniliforme. It is a contaminant of cereals, especially corn. It has been epidemiologically linked to high incidence of human esophageal cancer in South Africa and China and to hepatocarcinogenesis in animal models.

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Mechanism of Action
Fumonisins are inhibitors of the biosynthesis of sphingosine and more complex sphingolipids. In eucaryotic cells, fumonisin inhibition of sphingolipid biosynthesis is a result of inhibition of the enzyme ceramide synthase. Large increase in free sphinganine concentration in plant and animal cells are observed within a few hours after exposure to fumonisins and/or Alternaria toxins (AAL-toxins). Some of the sphinganine is metabolized to other bioactive intermediates, and some is released from cells. In animals, free sphinganine accumulates in tissues and quickly appears in blood and urine. Free sphingoid bases are toxic to most cells, and complex sphingolipids are essential for normal cell growth. Fumonisin B1 stimulates sphinganine-dependent DNA synthesis in Swiss 3T3 cells, but is mitoinhibitory in other cell types. In cultured cells the accumulation of bioactive long-chain sphingoid bases and depletion of complex sphingolipids are clearly contributing factors in growth inhibition, increased cell death, and (in Swiss 3T3 cells) mitogenicity of fumonisins. While disruption of sphingolipid metabolism directly affects cells, it may indirectly affect some tissues. For example, fumonisin B1 impairs the barrier function of endothelial cells in vitro. Adverse effects on endothelial cells could indirectly contribute to the neurotoxicity and pulmonary edema caused by fumonisins. It is hypothesized that fumonisin-induced changes in the sphingolipid composition of target tissues could directly or indirectly contribute to all Fusarium moniliforme-associated diseases.
Fumonisins are inhibitors of sphinganine (sphingosine) N-acyltransferase (ceramide synthase) in vitro, and exhibit competitive-type inhibition with respect to both substrates of this enzyme (sphinganine and fatty acyl-CoA). Removal of the tricarballylic acids from fumonisin B1 reduces the potency by at least 10 fold; and fumonisin A1 (which is acetylated on the amino group) is essentially inactive. Studies with diverse types of cells (hepatocytes, neurons, kidney cells, fibroblasts, macrophages, and plant cells) have established that fumonisin B1 not only blocks the biosynthesis of complex sphingolipids; but also, causes sphinganine to accumulate. Some of the sphinganine is metabolized to the 1-phosphate and degraded to hexadecanal and ethanolamine phosphate, which is incorporated into phosphatidylethanolamine. Sphinganine is also released from cells and, because it appears in blood and urine, can be used as a biomarker for exposure. The accumulation of these bioactive compounds, as well as the depletion of complex sphingolipids, may account for the toxicity, and perhaps the carcinogenicity, of fumonisins.
Fumonisin B1 produced by the fungus Fusarium moniliforme is a member of a new class of sphinganine analogue mycotoxins that occur widely in the food chain. Epidemiological studies associate FB1 with human sophageal cancer in China and South Africa. FB1 also causes acute pulmonary edema in pigs and equine leucoencephalomalacia. This disease is thought to be a consequence of inhibition by FB1 of cellular ceramide synthesis in cells. To investigate further on this pathogenesis, the effect of FB1 was studied on cell viability (3 to 54 uM of FB1), protein (2.5 to 20 uM of FB1) and DNA syntheses (2.5 to 50 uM of FB1), and cellular cycle (3 to 18 uM of FB1) of rat C6 glioma cells after 24 hr incubation. The results of the viability test show that FB1 induces 10 2% and 47 4% cell death with, respectively, 3 and 54 uM, in C6 cells. This cytotoxicity induced by FB1 was efficiently prevented when the cells were preincubated 24 hr with vitamin E (25 uM). FB1 displays epigenetic properties since it induced hypermethylation of the DNA (9-18 uM). Inhibition of protein synthesis was observed with FB1 with an IC50 of 6 M showing that C6 glioma cells are very sensitive to FB1; however, the synthesis of DNA was only slightly inhibited, up to 20 uM of FB1. The flow cytometry showed that the number of cells in phase S decreased significantly as compared to the control p = 0.01 from 18.7 2.5% to 8.1 1.1% for 9 uM FB1. The number of cells in phase G2/uM increased significantly as compared to the control (p 0.05) from 45.7 0.4% to 54.8 1.1% for 9 uM FB1, whereas no change occurs in the number of cells in the phase G0/G1. These results show that cytotoxic concentrations of FB1 induce cellular cycle arrest in phase G2/uM in rat C6 glioma cells possibly in relation with genotoxic events.
The molecular mechanism of action of fumonisins is not known; however, these compounds bear a remarkable structural similarity to sphingosine, the long-chain (sphingoid) base backbone of sphingomyelin, cerebrosides, sulfatides, gangliosides and other sphingolipids. Sphingolipids are thought to be involved in the regulation of cell growth, differentiation and neoplastic transformation through participation in cell-cell communication and cell-substratum interactions and possibly through interactions with cell receptors and signalling systems. Incubation of rat hepatocytes with fumonisins B1 and B2 inhibited incorporation of (14)C serine into the sphingosine moiety of cellular sphingolipids, at an IC50 of 0.1 uM. In contrast, fumonisin B1 increased the amount of the biosynthetic intermediate, sphinganine, which suggests that fumonisins inhibit the conversion of (14)C-sphinganine to N-acyl-(14)C-sphinganines, a step that is thought to precede introduction of the 4,5-trans double bond of sphingosine. In agreement with this mechanism, fumonisin B1 inhibited the activity of sphingosine N-acyltransferase (ceramide synthase) in rat liver microsomes, with 50% inhibition at approximately 0.1 uM, and reduced the conversion of (3)H-sphingosine to (3)H-ceramide by intact hepatocytes. Fumonisin B1 (1 uM) almost completely inhibited (14)C sphingosine formation by hepatocytes.

C34H59NO15

721.82996

721.388

C, 56.57; H, 8.24; N, 1.94; O, 33.25

116355-83-0

Fumonisin B1-13C34;1217458-62-2

2733487

White to light yellow solid powder

1.3±0.1 g/cm3

924.9±65.0 °C at 760 mmHg

513.2±34.3 °C

0.0±0.6 mmHg at 25°C

1.528

2.2

8

16

31

50

1070

10

CCCC[C@@H](C)[C@H]([C@H](C[C@@H](C)C[C@@H](CCCC[C@H](C[C@@H]([C@H](C)N)O)O)O)OC(=O)C[C@@H](CC(=O)O)C(=O)O)OC(=O)C[C@@H](CC(=O)O)C(=O)O

UVBUBMSSQKOIBE-DSLOAKGESA-N

InChI=1S/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)

(2R,2'R)-2,2'-((((5R,6R,7S,9S,11R,16R,18S,19S)-19-amino-11,16,18-trihydroxy-5,9-dimethylicosane-6,7-diyl)bis(oxy))bis(2-oxoethane-2,1-diyl))disuccinic acid

HSDB 7077; RT013063; HSDB7077; fumonisin b1; 116355-83-0; fumonisin-B1; Macrofusine; fumonisin B(1); UNII-3ZZM97XZ32; 3ZZM97XZ32; CCRIS 4433; RT-013063; HSDB-7077; RT 013063; Macrofusine

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~16.67 mg/mL (~23.09 mM)

Solubility in Formulation 1: 18.5 mg/mL (25.63 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with heating and sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)