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DNA damage in astrocytes exposed to fumonisin B1
F Galvano1, A Campisi, A Russo
1Department of Agro-forestry, Environmental Science and Technology, University of Reggio Calabria, Italy.
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 microM) does not affect cell viability. Conversely, after 72 h of treatment, FB1 (50 and 100 microM) 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 microM 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.
Insights
Fumonisin B1 (FB1), a corn-produced toxin, induces apoptotic DNA damage and caspase-3 activity in rat astrocytes. This study suggests FB1
Area of Science:
- Toxicology
- Cell Biology
- Biochemistry
Background:
- Fumonisins, toxic metabolites from Fusarium fungi, contaminate corn globally.
- Fumonisin B1 (FB1) inhibits ceramide synthase, disrupting sphingolipid biosynthesis.
- FB1 causes accumulation of sphinganine (SA) and sphingosine (SO), leading to cell death, but downstream effectors are poorly understood.
Purpose of the Study:
- To investigate the downstream effects of FB1 exposure in rat astrocytes.
- To evaluate the involvement of oxygen free radicals, caspase-3 activity, and DNA damage in FB1-induced cell death signaling.
Main Methods:
- Rat astrocytes were exposed to varying concentrations of FB1 (10-100 microM) for different durations (48h, 72h, 6 days).
- Cell viability, DNA damage, caspase-3 activity, and HSP70 expression were assessed.
Main Results:
- FB1 treatment did not significantly affect astrocyte viability.
- FB1 (50 and 100 microM) induced DNA damage and increased caspase-3 activity after 72 hours.
- FB1 exposure elevated HSP70 expression at lower concentrations (10 and 50 microM) across treatment durations.
Conclusions:
- FB1 causes apoptotic-type DNA damage in rat astrocytes.
- The genotoxic potential of FB1 may be underestimated and warrants further investigation.
- FB1-induced cellular responses involve DNA damage and caspase-3 activation, highlighting its toxicological significance.