Fumonisins and Alternaria alternata lycopersici toxins

Sphinganine analog mycotoxins induce apoptosis in monkey kidney cells

Hong Wang, Clinton J Jones, Janice Ciacci-Zanella, Todd Holt, David G. Gilchrist, Martin B. Dickman

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

Fusarium moniliforme toxins (fumonisins) and Alternaria alternata lycopersici (AAL) toxins are members of a new class of sphinganine analog mycotoxins that occur widely in the food chain. These mycotoxins represent a serious threat to human and animal health, inducing both cell death and neoplastic events in mammals. The mechanisms by which this family of chemical congeners induce changes in cell homeostasis were investigated in African green monkey kidney cells (CV-1) by assessing the appearance of apoptosis, cell cycle regulation, and putative components of signal transduction pathways involved in apoptosis. Structurally, these mycotoxins resemble the sphingoid bases, sphingosine and sphinganine, that are reported to play critical roles in cell communication and signal transduction. The addition of fumonisin B1 or AAL toxin, TA, to CV-1 cells induced the stereotypical hallmarks of apoptosis, including the formation of DNA ladders, compaction of nuclear DNA, and the subsequent appearance of apoptotic bodies. Neither mycotoxin induced cell death, DNA ladders, or apoptotic bodies in CV-1 cells expressing simian virus 40 large T antigen (COS-7) at toxin concentrations that readily killed CV-1 cells. Fumonisin B1 induced cell cycle arrest in the G1 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 health risk to humans and livestock. These molecules also represent a new class of natural toxicants that can be used as model compounds in further characterize the molecular and biochemical pathways leading to apoptosis.

Original languageEnglish (US)
Pages (from-to)3461-3465
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number8
DOIs
StatePublished - Apr 16 1996

Fingerprint

Fumonisins
Alternaria
Mycotoxins
Haplorhini
Apoptosis
Kidney
Cell Cycle Checkpoints
Signal Transduction
DNA
Cell Death
Cercopithecus aethiops
Sphingosine
Food Chain
Simian virus 40
COS Cells
Viral Tumor Antigens
Health
Fusarium
G1 Phase
Livestock

Keywords

  • CV-1 cells
  • cancer
  • cell cycle
  • food safety
  • programmed cell death

ASJC Scopus subject areas

  • General

Cite this

Fumonisins and Alternaria alternata lycopersici toxins : Sphinganine analog mycotoxins induce apoptosis in monkey kidney cells. / Wang, Hong; Jones, Clinton J; Ciacci-Zanella, Janice; Holt, Todd; Gilchrist, David G.; Dickman, Martin B.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 8, 16.04.1996, p. 3461-3465.

Research output: Contribution to journalArticle

Wang, Hong ; Jones, Clinton J ; Ciacci-Zanella, Janice ; Holt, Todd ; Gilchrist, David G. ; Dickman, Martin B. / Fumonisins and Alternaria alternata lycopersici toxins : Sphinganine analog mycotoxins induce apoptosis in monkey kidney cells. In: Proceedings of the National Academy of Sciences of the United States of America. 1996 ; Vol. 93, No. 8. pp. 3461-3465.
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