We determined that cytotoxicity of fusarenon-X (FX), a trichohtecene mycotoxin, is due to apoptosis both in vitro and in vivo. FX induced nuclear fragmentation of thymocytes (TUNEL staining and electron microscopy) in the thymic cortex in mice at a dose of 4.5 mg/kg or higher. DNA ladder patterns of 180 bp multimers were apparent in thymocytes both from these mice and those cultured with 0.5-1.0 microgram/ml of FX (agarose gel electrophoresis). Flowcytometric analysis of human promyelocytic cell line HL-60 exposed to FX showed an increment in the apoptotic population. This increment was inhibited by pre-treatment with ZnCl2 (inhibitor of DNase) or Z-Asp-CH2-DCB (inhibitor of caspase). Caspase-3 and -8 in the cytosol of HL-60 were activated 2 hours after exposure to FX. These results indicate that apoptotic mechanisms are involved in the toxicity of trichothecene mycotoxin fusarenon-X to animals. (Associate Director for Research, Department of Feed Safety TEL +81-298-38-7819)
References:
1. Miura, K., et al.: Induction of apoptosis with fusarenon-X in mouse thymocytes. Toxicology, 127 : 195-206 (1998)
