DNA damage in astrocytes exposed to fumonisin B1

Fumonisins are a group of toxic metabolites mainly produced by Fusarium moniliforme and Fusarium proliferatum, fungi that commonly occur on corn throughout the world. Fumonisin B-1 (FB1), structurally resembling sphingoid bases, is an inhibitor of ceramide synthase, 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 (SA) and sphingosine (SO), inducing cell death. However, little is known on the down stream effectors activated by these sphingolipids in the cell death signaling pathway. We exposed rat astrocytes to FB1 with the aim of evaluating the involvement of oxygen free radicals and of some other biochemical pathways such as caspase-3 activity and DNA damage. Our results indicate that FB1 treatment (48, 72 h and 6 days in vitro. DIV, and 10, 50, 100 muM) does not affect cell viability. Conversely, after 72 h of treatment, FB1 (50 and 100 muM) induced DNA damage and an enhancement of caspase-3 activity compared to controls. In addition, FBI increased the expression of HSP70 at 10 and 50 muM at 48, 72 h, and 6 DIV of treatment. We conclude that DNA damage of apoptotic type in rat astrocytes is caused by FBI and that the genotoxic potential of FB1 has probably been underestimated and should be reconsidered.