No abstract

The filamentous ascomycete Fusarium verticillioides is a pathogen of maize and produces the fumonisin mycotoxins. However, a distinct population of F. verticillioides is pathogenic on banana and does not produce fumonisins. Fumonisin-producing strains from maize cause leaf lesions, developmental abnormalities, stunting, and sometimes death of maize seedlings, whereas fumonisin-nonproducing banana strains do not. A Southern analysis of banana strains did not detect genes in the fumonisin biosynthetic gene (FUM) cluster but did detect genes flanking the cluster. Nucleotide sequence analysis of the genomic region carrying the flanking genes revealed that the FUM cluster was absent in banana strains except for portions of FUM21 and FUM19, which are the terminal genes at each end of the cluster. Polymerase chain reaction analysis confirmed the absence of the cluster in all banana strains examined. Cotransformation of a banana strain with two overlapping cosmids, which together contain the entire FUM cluster, yielded fumonisin-producing transformants that were pathogenic on maize seedlings. Conversely, maize strains that possess the FUM cluster but do not produce fumonisins because of mutations in FUM1, a polyketide synthase gene, were not pathogenic on maize seedlings. Together, the data indicate that fumonisin production may have been lost by deletion of the FUM cluster in the banana population of F. verticillioides but that fumonisin production could be restored by molecular genetic complementation. The results also indicate that fumonisin production by F. verticillioides is required for development of foliar disease symptoms on maize seedlings.

In Jutiapa, agroecological conditions favored FB production. UFB1 mirrored the estimated FB intake. UFB1 > 0.1 ng/mL resulted in a dose-dependent increase in the risk of exceeding FB intake of 2 μg/kg b.w./day compared to women with no detectable UFB1 . More than 50% exceeded 2 μg/kg b.w./day when UFB1 was >0.5 ng/mL. UFB2 and UFB3 were rarely detected confirming that FB1 is either absorbed better or preferentially excreted in urine.

Fumonisins (FB) are mycotoxins found in maize. The purpose of this study was to 1) determine the relationship between FB1, FB2 and FB3 intake and urinary excretion in humans, 2) validate a method to isolate urinary FB on C18-SPE cartridges for international shipment, and 3) test the method using samples from Guatemala. Volunteers (n=10) consumed 206 grams/day of tortillas and biscuits prepared from masa flour and a product containing maize flour. Volunteers estimated their daily urine output and samples were analyzed for FB1, FB2 and FB3 and hydrolyzed FB1. Only FB1 was detected in urine suggesting lower absorption of FB2 and FB3. Excretion was highly variable peaking soon after consumption began and decreasing rapidly after consumption stopped. Within five days after consumption ended FB1 was not detected in urine. In a study with eight volunteers, the average total urinary FB1 was 0.5% of the intake. FB1 was detected in 61% (107/177) of the samples collected in Guatemala. The results support the use of urinary FB1 to assess ongoing exposure in population based studies. However, relating the FB1 concentration in urine to dietary intake of FB by individual subjects will be complicated due to inter-individual variability and the rapidity of clearance.

13 C]deoxySa. 1-DeoxySa was elevated in FB 1 -treated cells and mouse liver and kidney, and its cytotoxicity was greater than or equal to that of Sa for LLC-PK 1 and DU-145 cells. Therefore, this compound is likely to contribute to pathologies associated with fumonisins. In the absence of FB 1 , substantial amounts of 1-deoxySa are made and acylated to N-acyl-1-deoxySa (i.e. 1-deoxydihydroceramides). Thus, these compounds are an underappreciated category of bioactive sphingoid bases and "ceramides" that might play important roles in cell regulation. Fumonisins (FB)2 cause diseases of horses, swine, and other farm animals and are regarded to be potential risk factors for human esophageal cancer (1) and, more recently, birth defects (2). Studies of this family of mycotoxins, and particularly of the highly prevalent subspecies fumonisin B 1 (FB 1 ) (reviewed in Refs. 1 and 2), have established that FB 1, is both toxic and carcinogenic for laboratory animals, with the liver and kidney being the most sensitive target organs (3, 4). Other FB are also toxic, but their carcinogenicity is unknown.FB are potent inhibitors of ceramide synthase(s) (CerS) (5), the enzymes responsible for acylation of sphingoid bases using fatty acyl-CoA for sphingolipid biosynthesis de novo and recycling pathways (6). As a consequence of this inhibition, the substrates sphinganine (Sa) and, usually to a lesser extent, sphingosine (So), accumulate and are often diverted to sphinganine 1-phosphate (Sa1P) and sphingosine 1-phosphate (S1P), respectively (7), while the product N-acylsphinganines (dihydroceramides), N-acylsphingosines (ceramides, Cer), and more complex sphingolipids decrease (5, 7). This disruption of sphingolipid metabolism has been proposed to be responsible for the toxicity, and possibly carcinogenicity, of FB, based on mechanistic studies with cells in culture (5,(7)(8)(9). This has been borne out by a number of animal feeding studies that have correlated the elevation of Sa in blood, urine, liver, and kidney with liver and kidney toxicity (4, 7, 10, 11).Most of the mechanistic studies have focused on the accumulation of free Sa and other sphingoid bases, because these compounds are highly cytotoxic, although the large number of bioactive metabolites in this pathway make it likely that multi-