FUMONISINS AND ALTERNARIA-ALTERNATA LYCOPERSICI TOXINS - SPHINGANINE ANALOG MYCOTOXINS INDUCE APOPTOSIS IN MONKEY KIDNEY-CELLS

Fusarium moniliforme toxins (fumonisins) and Alfernaria alternata lyco persici (AAL) toxins are members of a new class of sphinganine analog mycotoxins that occur widely in the food chain, These mycotoxins repre sent a serious threat to human and animal health, inducing both cell d eath and neoplastic events in mammals, The mechanisms by which this fa mily of chemical congeners induce changes in cell homeostasis were inv estigated in African green monkey kidney cells (CV-1) by assessing the appearance of apoptosis, cell cycle regulation, and putative componen ts of signal transduction pathways involved in apoptosis, Structurally , these mycotoxins resemble the sphingoid bases, sphingosine and sphin ganine, that are reported to play critical roles in cell communication and signal transduction, The addition of fumonisin B-1 or AAL toxin, TA, to CV-1 cells induced the stereotypical hallmarks of apoptosis, in cluding the formation of DNA ladders, compaction of nuclear DNA, and t he subsequent appearance of apoptotic bodies, Neither mycotoxin induce d cell death, DNA ladders, or apoptotic bodies in CV-1 cells expressin g simian virus 40 large T antigen (COS-7) at toxin concentrations that readily killed CV-1 cells. Fumonisin B-1 induced cell cycle arrest in the G(1) phase in CV-1 cells but not in COS-7 cells, AAL toxin TA did not arrest cell cycle progression in either cell line, The induction of apoptosis combined with the widespread presence of these compounds in food crops and animal feed identifies a previously unrecognized hea lth risk to humans and livestock, These molecules also represent a new class of natural toxicants that can be used as model compounds to fur ther characterize the molecular and biochemical pathways leading to ap optosis.