Fumonisins are mycotoxins produced by several Fusarium species (Fusarium verticilloides and F. proliferatum) that infest corn and other cereals. Fumonisin B1 (FB1), structurally resembling sphingoid bases, is an inhibitor of ceramide synthetase, a key enzyme involved in de novo sphingolipid biosynthesis and in the reacylation of free sphingoid bases derived from sphingolipid turnover. This inhibitory effect leads to accumulation of free sphinganine and sphingosine and subsequent induction of cell death. However, the downstream effectors activated by these sphingolipids in the cell death-signalling pathway are little known. The aim of this study was to evaluate, in FB1-exposed human fibroblasts, the involvement of oxygen free radicals and of some other biochemical pathways, caspase-3 activity, poly(ADP-ribose)polymerase (PARP) cleavage and DNA damage evaluated by comet assay. Our results indicate that FB1 treatment (48, 72 h and 10, 50, 100 μM) does not affect cellular viability. Conversely, after 72 h of treatment, FB1 (50 and 100 μM) induced DNA damage, an enhancement of caspase-3-activity and cleavage of PARP compared to controls. In addition, FB1 increased the expression of HSP70 in a concentration and time-dependent manner. Our results indicate that DNA damage of apoptotic type in human fibroblasts is caused by exposure to FB1 at high concentrations and for a prolonged time and that the genotoxic potential of FB1 has probably been underestimated and should be reconsidered.

DNA damage in human fibroblast exposed to fumonisin B1

GALVANO, Fabio;RUSSO, Alessandra;CARDILE, Venera;GALVANO, Giacomo;VANELLA, Angelo;Renis, M.
2002

Abstract

Fumonisins are mycotoxins produced by several Fusarium species (Fusarium verticilloides and F. proliferatum) that infest corn and other cereals. Fumonisin B1 (FB1), structurally resembling sphingoid bases, is an inhibitor of ceramide synthetase, a key enzyme involved in de novo sphingolipid biosynthesis and in the reacylation of free sphingoid bases derived from sphingolipid turnover. This inhibitory effect leads to accumulation of free sphinganine and sphingosine and subsequent induction of cell death. However, the downstream effectors activated by these sphingolipids in the cell death-signalling pathway are little known. The aim of this study was to evaluate, in FB1-exposed human fibroblasts, the involvement of oxygen free radicals and of some other biochemical pathways, caspase-3 activity, poly(ADP-ribose)polymerase (PARP) cleavage and DNA damage evaluated by comet assay. Our results indicate that FB1 treatment (48, 72 h and 10, 50, 100 μM) does not affect cellular viability. Conversely, after 72 h of treatment, FB1 (50 and 100 μM) induced DNA damage, an enhancement of caspase-3-activity and cleavage of PARP compared to controls. In addition, FB1 increased the expression of HSP70 in a concentration and time-dependent manner. Our results indicate that DNA damage of apoptotic type in human fibroblasts is caused by exposure to FB1 at high concentrations and for a prolonged time and that the genotoxic potential of FB1 has probably been underestimated and should be reconsidered.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11769/1203
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