INDUCTION OF APOPTOSIS WITH FUSARENON-X IN MOUSE THYMOCYTES

The effects of fusarenon-X (12,13-epoxytrichothecene; FX) on mouse thy mus and T-cell subpopulations were studied. In mice that received thre e intraperitoneal injections of FX, the thymus showed severe atrophy, the thymic cortex almost completely disappeared, and the total number of thymocytes decreased to 2.2% of that of normal mice. CD4(+)CD8(+) t hymocytes were almost completely depleted by this treatment while CD4( +)CD8(-), CD4(-)CD8(+) and CD4(-)CD8(-) thymocytes were not reduced to such an extent, suggesting that selective damage in CD4(+)CD8(+) thym ocytes was induced by FX. In spleen, CD4(+) or CD8(+) lymphocytes and CD4(-)CD8(-) non-T cells remained unchanged. Next, the mode of damage in thymocytes was investigated by a single injection with FX. The lymp hocyte nuclei were fragmented and positive for TUNEL (TdT-mediated dUT P nick-end labeling) staining in the thymic cortex 20 h after FX injec tion. By electron microscopy, apoptotic lymphocytes with condensed nuc lei and stroma cells ingesting many nuclear fragments were frequently observed in the thymic cortex. Internucleosomal DNA fragmentation was apparent in the thymocytes treated with FX both in vivo and in vitro. Thus, we demonstrated that the trichothecene mycotoxin FX is a new cau se of apoptosis in CD4(+)CD8(+) thymocytes of mice besides the other f actors that cause similar effects. (C) 1998 Elsevier Science Ireland L td. All rights reserved.