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DNA Damage in Astrocytes Exposed to Fumonisin B1

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Abstract

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 B1 (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 μM) does not affect cell viability. Conversely, after 72 h of treatment, FB1 (50 and 100 μM) induced DNA damage and an enhancement of caspase-3 activity compared to controls. In addition, FB1 increased the expression of HSP70 at 10 and 50 μM at 48, 72 h, and 6 DIV of treatment. We conclude that DNA damage of apoptotic type in rat astrocytes is caused by FB1 and that the genotoxic potential of FB1 has probably been underestimated and should be reconsidered.

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Authors and Affiliations

  1. Department of Agro-forestry, Environmental Science and Technology, University of Reggio Calabria, P.zza S. Francesco 7, Reggio Calabria, Italy

    F. Galvano

  2. Department of Biochemistry, Medical Chemistry and Molecular Biology, University of Catania, V.le A. Doria 6, Catania, Italy

    A. Campisi, A. Russo, M. Palumbo, M. Renis & M. L. Barcellona

  3. Department of Agronomy, Chemistry and Animal Production, University of Catania, Via Valdisavoia 5, Catania, Italy

    G. Galvano

  4. Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, 432 Gail Borden F52, Galveston, TX, 77550-2777

    J. R. Perez-Polo

  5. Department of Biochemistry, Medical Chemistry and Molecular Biology, University of Catania, V.le A. Doria 6, Catania, Italy

    A. Vanella

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Galvano, F., Campisi, A., Russo, A. et al. DNA Damage in Astrocytes Exposed to Fumonisin B1. Neurochem Res 27, 345–351 (2002). https://doi.org/10.1023/A:1014971515377

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