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
Fusarium B1 (FB1) is a major compound in the secondary metabolites of Fusarium moniliforme Sheldon and is associated with certain human and animal diseases. Following intraperitoneal injection of FB1 (7.5 mg/kg) in rats, FB1 is rapidly absorbed, reaching peak plasma concentrations within 20 minutes. Subsequently, FB1 is rapidly cleared from plasma following a single-exponential elimination process consistent with a one-compartment model, with a half-life of 18 minutes. Urine samples collected at 24 and 48 hours showed that only 16% of the administered dose was excreted in the urine as unmetabolized form, all within 24 hours of administration. In contrast, after gavage administration of the same dose of FB1, only 0.4% of FB1 was recovered in the urine. Fumonisin B1 (FB1) is a toxic and carcinogenic secondary metabolite produced by Fusarium moniliforme Sheldon. In this study, it was administered to African green monkeys (Cercopithecus aethiops) via intravenous injection or gavage. Following intravenous injection in two female African green monkeys, FB1 was rapidly cleared from the plasma, with a mean elimination half-life of 40 minutes. Analysis of urine and feces within 5 days post-administration showed a mean recovery rate of 47% for FB1 and its hydrolyzed analogues. Two additional female African green monkeys received a single gavage administration of 14C-labeled FB1. Over the following 3 days, the average excretion of radioactive material in feces was 61% of the administered dose, and in urine, it was 1.2%. Small amounts of residual radioactive material were recovered from skeletal muscle (1%), liver (0.4%), brain (0.2%), kidney, heart, plasma, erythrocytes, and bile (all 0.1%), while intestinal contents accounted for 12% of the radioactive dose. A total of 76% of the administered radioactive material was recovered. Analysis of feces, intestinal contents, and urine showed that over 90% of the radioactive material in these samples originated from fumonisin B1 and its hydrolysis products. A method for determining fumonisin B1 (FB1) in the feces of non-human primates (long-tailed macaques) has been developed. After injecting animals with FB1 labeled with 14C, the feces were repeatedly extracted with 0.1 M ethylenediaminetetraacetic acid (EDTA). The extract was purified using a reversed-phase (C18) solid-phase extraction column, and FB1 was determined by phthalaldehyde derivatization and reversed-phase high-performance liquid chromatography (RP-HPLC). The analytical method for FB1 in fecal extract showed good reproducibility (relative standard deviation (RSD) of 2.6%) and high accuracy (recovery of spiked blank extract was 93 ± 2.9% RSD). High performance liquid chromatography (HPLC) and thin-layer chromatography (TLC) were used to further confirm the presence of FB1 in feces. The results showed that the extracted radioactive substances were mainly FB1 and a novel metabolite, whose chromatographic properties were similar to those of the fungal toxin. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) analysis identified a novel metabolite as an equilibrium mixture of two structural isomers of partially hydrolyzed fumonisin B1 (FB1), formed by the hydrolysis of one ester group of the fungal toxin. The fungal toxin fumonisin B1 (FB1) can cause various health problems in animals, and epidemiological evidence suggests its association with esophageal cancer in humans. We investigated the residue of FB1 in milk using an in vitro bovine udder perfusion model. 2 mg of FB1 was injected into the perfused blood from three udders, and the FB1 levels in milk and perfused serum were measured within 150 minutes. The results showed that FB1 could cross the mammary gland barrier and enter milk, but the concentration was extremely low, and the risk to consumers was negligible.

Toxicity Summary
Identification: Fumonisin B1 is the most common fumonisin, produced by Fusarium moniliforme and other Fusarium fungi. The pure substance is a white, hygroscopic powder, soluble in water, acetonitrile-water, and methanol. It is stable under food processing temperatures and light. Fumonisin B1 is the most common fungal metabolite associated with corn. It accumulates significantly in corn when climatic conditions are favorable for kernel decay. Human Exposure: No acute toxicity associated with this compound has been recorded. Existing correlational studies suggest an association between dietary exposure and esophageal cancer. Other studies have not reached a definitive conclusion regarding the potential carcinogenicity of fumonisin B1. Animal/Plant Studies: Fumonisin B1 is hepatotoxic in all tested animal species, including mice, rats, equines, pigs, rabbits, and non-human primates. Except for Syrian hamsters, embryotoxicity or teratogenicity occurs only during or after maternal toxicity. Fumonisin is nephrotoxic in pigs, rats, sheep, mice, and rabbits. In rats and rabbits, the nephrotoxic dose is lower than the hepatotoxic dose. Fumonisin is known to cause leukomalacia in equines and pulmonary edema syndrome in pigs. It is hepatocarcinogenic in one strain of male rats and renal carcinogenic in another strain. Fumonisin B1 is a specific inhibitor of de novo sphingolipid synthesis. This compound inhibits cell growth, leading to the accumulation of free sphingosine bases and altering lipid metabolism in animals, plants, and certain yeasts (such as Saccharomyces cerevisiae). This compound does not induce bacterial gene mutations or unplanned DNA synthesis in primary rat hepatocytes, but it induces chromosomal aberrations at low concentrations in a dose-dependent manner. This compound is phytotoxic, damaging cell membranes and reducing chlorophyll synthesis. Based on studies in pigs, laying hens, and long-tailed monkeys, this compound has low oral absorption and is rapidly cleared from the plasma or circulatory system and excreted in feces; bile excretion is important; enterohepatic circulation is also important in some animals. Small amounts of the compounds are excreted in urine, while some remain in the liver and kidneys. The Committee reviewed studies available since the last assessment in 2011 and concluded that these studies do not alter the Committee's previous overall toxicological assessment. Therefore, the Committee maintains the previously established PMTDI for FB1, FB2, and FB3 (alone or in combination) at 2 µg/kg body weight. The Committee notes that the international exposure estimates for FB1 and total fumonisins in this assessment are lower than those given at the Committee's seventy-fourth session in 2011. Compared to 2011, this assessment includes a higher proportion of incidence data from WHO European Region countries, resulting in a lower overall level of fumonisins in maize. Data on fumonisin levels in maize from countries in the African, Eastern Mediterranean, and Southeast Asian Regions are missing in this assessment, where higher concentrations of fumonisins are typically detected. Given these limitations of the incidence data used in this exposure assessment, and the fact that the literature reports high exposure levels in some countries, the actual fumonisin exposure levels in areas where maize is a staple food and fumonisin contamination is severe may be higher than the Committee's estimates at this meeting, as previous assessments have shown, based on larger, more representative datasets. At its eighty-third meeting, the Committee also assessed the co-exposure to aflatoxin and fumonisin. Both fumonisin and aflatoxin are common contaminants in cereals and cereal products. Aflatoxin is a common contaminant in peanuts and nuts. In areas where these foods are frequently consumed, people are likely to be exposed to both mycotoxins simultaneously. Although previous and current evidence from laboratory animals suggests that co-exposure to fumonisin and aflatoxin has an additive or synergistic effect in the development of precancerous lesions or hepatocellular carcinoma, there are currently no data on such effects in humans. The Committee concludes that the available data offer little support for co-exposure as a contributing factor to human disease. However, the interaction between aflatoxin B1 (AFB1), a compound known to be genotoxic, and fumonisin, which has the potential to induce regenerative cell proliferation (especially at exposure levels above the average daily tolerable intake), remains a concern. This is because in some parts of the world, the incidence of chronic liver disease and developmental delays is high, and co-exposure to these two mycotoxins is also high in these areas, with biomarkers confirming co-exposure to both toxins.

[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.

According to the International Agency for Research on Cancer (IARC) of the World Health Organization and the National Toxicology Program (NTP) of the United States, fumonisin B1 is carcinogenic. Fumonisin B1 is a diester formed by the condensation of the 1-carboxyl group of two molecules of propane-1,2,3-tricarboxylic acid with the hydroxyl groups at positions 14 and 15 of (2S,3S,5R,10R,12S,14S,15R,16R)-2-amino-12,16-dimethyleicosano-3,5,10,14,15-pentanol. It is both a metabolite and a carcinogen. It is a fumonisin, a primary amino compound, a diester, and a triol. Functionally, it is associated with (2S,3S,5R,10R,12S,14S,15R,16R)-2-amino-12,16-dimethyleicosano-3,5,10,14,15-pentanol. It is the conjugate acid of fumonisin B1(3-). Fumonisin macrocarpa has been reported in Streptomyces and Arabidopsis thaliana, with relevant data. Fumonisin B1 is a fungal toxin produced by Fusarium moniliforme. It is a contaminant in cereals, especially maize. Epidemiological studies have shown its association with high incidence of esophageal cancer in humans in South Africa and China, as well as liver cancer in animal models. Mechanism of Action Fumonisin is an inhibitor of sphingosine and the more complex sphingolipid biosynthesis. In eukaryotic cells, fumonisin inhibits sphingolipid biosynthesis by inhibiting the activity of ceramide synthase. Within hours of exposure to fumonisin and/or Alternaria toxin (AAL toxin), free sphingosine concentrations significantly increase in plant and animal cells. Some sphingosine is metabolized into other bioactive intermediates, while some is released from the cells. In animals, free sphingosine accumulates in tissues and rapidly appears in blood and urine. Free sphingosine bases are toxic to most cells, while complex sphingolipids are essential for normal cell growth. Fumonisin B1 stimulates sphingosine-dependent DNA synthesis in Swiss 3T3 cells, but has mitochondrial inhibitory effects in other cell types. In cultured cells, the accumulation of bioactive long-chain sphingosine bases and the depletion of complex sphingolipids are clearly factors contributing to growth inhibition, increased cell death, and (in Swiss 3T3 cells) fumonisin-induced mitosis. Disorders of sphingolipid metabolism not only directly affect cells but may also indirectly affect certain tissues. For example, fumonisin B1 impairs the barrier function of endothelial cells in vitro. Adverse effects on endothelial cells may indirectly lead to fumonisin-induced neurotoxicity and pulmonary edema. It is speculated that fumonisin-induced changes in target tissue sphingolipid composition may directly or indirectly contribute to all diseases associated with Fusarium moniliforme. Fumonisin is an inhibitor of sphingosine N-acyltransferase (ceramide synthase) in vitro, exhibiting competitive inhibition of both substrates of this enzyme (sphingosine and fatty acyl-CoA). Removing the tricarboxylic acid group from fumonisin B1 reduces its potency by at least 10-fold; while fumonisin A1 (aminoacetylated) is essentially inactive. Studies on various cell types (hepatocytes, neurons, kidney cells, fibroblasts, macrophages, and plant cells) have shown that fumonisin B1 not only blocks the biosynthesis of complex sphingolipids but also leads to the accumulation of sphingosine. Some sphingosine is metabolized to 1-phosphate esters and degraded into hexadecaldehyde and phosphoethanolamine, the latter being incorporated into phosphatidylethanolamine. Sphingosine is also released from cells and, due to its presence in blood and urine, can be used as a biomarker of exposure. The accumulation of these bioactive compounds and the depletion of complex sphingolipids may be the cause of fumonisin toxicity (and perhaps carcinogenicity). Fumonisin B1, produced by Fusarium moniliforme, is a novel sphingosine analog fungal toxin widely distributed in the food chain. Epidemiological studies have shown that fumonisin B1 is associated with esophageal cancer in humans in China and South Africa. Fumonisin B1 also causes acute pulmonary edema in pigs and leukomalacia in equines. These diseases are believed to be caused by FB1 inhibiting intracellular ceramide synthesis. To further investigate its pathogenesis, this study examined the effects of FB1 concentrations (3–54 μM) on the viability, protein synthesis (2.5–20 μM), DNA synthesis (2.5–50 μM), and cell cycle (3–18 μM) of rat C6 glioma cells. Experiments were conducted after 24 hours of incubation. Viability tests showed that FB1 concentrations of 3 μM and 54 μM resulted in C6 cell mortality rates of 10.2% and 47.4%, respectively. Pre-incubation of cells with vitamin E (25 μM) for 24 hours effectively inhibited FB1-induced cytotoxicity. FB1 possesses epigenetic properties as it induces DNA hypermethylation (9-18 μM). FB1 inhibits protein synthesis with an IC50 of 6 μM, indicating that C6 glioma cells are highly sensitive to FB1; however, DNA synthesis was only slightly inhibited at FB1 concentrations as high as 20 μM. Flow cytometry analysis showed that, compared with the control group, the number of S-phase cells in the 9 μM FB1 treatment group was significantly reduced (p = 0.01), decreasing from 18.7 ± 2.5% to 8.1 ± 1.1%. Compared with the control group, the number of G2/μM phase cells in the 9 μM FB1 treatment group was significantly increased (p < 0.05), increasing from 45.7 ± 0.4% to 54.8 ± 1.1%, while the number of G0/G1 phase cells remained unchanged. These results indicate that cytotoxic concentrations of FB1 can induce G2/μM phase cell cycle arrest in rat C6 glioma cells, which may be related to genotoxic events. The molecular mechanism of action of fumonisins is unclear; however, these compounds share significant structural similarities with sphingosine, the long-chain (sphingosine) backbone of sphingolipids, cerebrosides, thiolipins, gangliosides, and other sphingolipids. Sphingolipids are thought to be involved in the regulation of cell growth, differentiation, and tumor transformation, and their mechanisms may include involvement in intercellular communication and cell-matrix interactions, and possibly through interactions with cell receptors and signaling systems. Incubation of rat hepatocytes with fumonisins B1 and B2 inhibited the incorporation of (14)C serine into the sphingosine moiety of cellular sphingolipids, with an IC50 value of 0.1 μM. Conversely, fumonisin B1 increased the content of the biosynthetic intermediate sphingosine, indicating that fumonisin inhibits the conversion of (14)C-sphingosine to N-acyl-(14)C-sphingosine, a step thought to precede the introduction of the 4,5-trans double bond of sphingosine. Consistent with this mechanism, fumonisin B1 inhibited the activity of sphingosine N-acyltransferase (ceramide synthase) in rat liver microsomes by 50% at a concentration of approximately 0.1 μM, and reduced the conversion of (3)H-sphingosine to (3)H-ceramide in intact hepatocytes. Fumonisin B1 (1 μM) almost completely inhibited the production of (14)C-sphingosine in 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.)