Induction of apoptosis with fusarenon-X in mouse thymocytes.

The effects of fusarenon-X (12,13-epoxytrichothecene; FX) on mouse thymus and T-cell subpopulations were studied. In mice that received three 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+ thymocytes 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+ thymocytes 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 lymphocyte nuclei were fragmented and positive for TUNEL (TdT-mediated dUTP nick-end labeling) staining in the thymic cortex 20 h after FX injection. By electron microscopy, apoptotic lymphocytes with condensed nuclei 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 cause of apoptosis in CD4+ CD8+ thymocytes of mice besides the other factors that cause similar effects.