Mode of action of trichothecenes

Abstract

In the present discussion, the author summarized the toxicological and biological features of thirty kinds of trichothecene mycotoxins which are produced by a wide range of Fusarium, Myrothecium and others. The 12, 13-epoxytrichothecenes induce nausea, vomiting, skin inflammation, leukopenia, diarrhea, haemorrhage in lung and brain, and destruction of bone marrow. Since these toxicological characteristics coincide with a major symptom of intoxicated humans and farm animals induced by consumption of moldy cereals and feeds, the red-mold toxicosis and bean-hulls poisoning in Japan, moldy corn toxicosis in USA, alimentary toxic aleukia (ATA), stachybotryotoxicosis and dendrodochiotoxicosisin Europe, are originated from a common toxicant, trichothecenes. Orally administered trichothecenes are rapidly absorped and eliminated into the feces and urine upon deacylation at C-4 and C-8 by the microsomal esterase and others. Biochemical approaches to the mode of action revealed that the trichothecenes are a potent inhibitor of protein and DNA syntheses in eukaryotic cells. Binding to the eukaryotic polysomes and ribosomes and the subsequent inactivation of ribosomal cycle is responsible for their inhibitory effect to initiation and termination reactions. Microbial approaches revealed that the trichothecenes are mutagenic to yeast cells, but are negative in DNA-attacking ability to Bacillus subtilis and reversion assay with Salmonella typhimurium. Reactivity of the epoxide ring of trichothecenes with SH-group of proteins will be discussed in relation to the molecular mechanism of action. © 1977, Walter de Gruyter. All rights reserved.