Hiroki Okumura, Naoto Yoshino, Yoshitsugu Sugiura, Masao Sugamata, Eeva-liisa Hintikka, Bruce Jarvis, Yoshio Ueno

Department of Toxicology and Microbial Chemistry, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Ichigaya, E-mail youeno@kagu.sut.ac.jp

Induction of apoptosis by the trichothecenes was examined in promyelotic leukemia cell line HL-60 and mice. An early elevation of intracellular Ca++ ion followed by disruption of observed mitochondrial transmembrane potential, induction of caspase-3, and DNA fragmentaion was oberved in T-2 toxin-treated cells. An induction of apoptotic cell death in the tissues of mice given T-2 toxin was confirmed by electron microscopic analysis. The induction of apoptosis was proposed as a novel cell death mechanism of T-2 toxin as well as macrocyclic trichothecenes.