Comparison of toxicity induced by T-2 toxin on human and rat granulo-monocytic progenitors with an in vitro model

Abstract

T-2 toxin is a trichothecene mycotoxin produced by various species of fungi. Trichothecenes are known as major contaminants of cereals and their derivatives. In man as well as in animals, T-2 toxin has been shown to induce alimentary intoxication and, among others, haematological symptoms. Granulo-monocytic progenitors from human umbilical cord blood on the one hand and granulo-monocytic progenitors from rat bone marrow on the other, were cultured in the presence of T-2 toxin (from 10(-7) to 10(-10) M) for 14 days. A study of concentration and effect relationships showed a strong and rapid effect of T-2 toxin on rat colony forming unit-granulocyte and macrophage (CFU-GM) between 5 x 10(-9) M and 10(-9) M. On the other hand, human CFU-GM were able to grow in the presence of the same T-2 toxin concentrations. IC50 were determined on day 7, 10 and 14. They were, respectively, 1.6 x 10(-9) M; 3.6 x 10(-9) M; 1.4 x 10(-9) M for human cells, and 2.2 x 10(-9) M; 3.3 x 10(-9) M; 2.6 x 10(-9) M for rat cells. The present study was prompted by the need to define precisely the cytotoxic and inhibitory T-2 toxin concentrations for rat and human CFU-GM. It is particularly relevant for the investigation of cellular T-2 toxin targets and in order to elucidate the mechanism of trichothecene haematotoxicity.