Induction of DNA single-strand breaks by T2 toxin, a trichothecene metabolite of fusarium: effect on lymphoid organs and liver.

T2 toxin, a trichothecene metabolite produced by Fusarium species, contaminates cereals harvested and stored under damp and cold conditions. These substances are responsible for Alimentary Toxic Aleukia (ATA), a severe human disease, and numerous animal intoxications. The action of T2 toxin on DNA was studied by using Parodi's alkaline elution technique coupled with a microfluorimetric determination of DNA. In vivo the effect of the toxin was studied on liver, spleen and thymus, and in vitro on a primary culture of rat hepatocytes and on splenic and thymic lymphocytes stimulated by PHA. Under our experimental conditions, in vivo and in vitro, no damage was observed for the hepatic DNA. By contrast, the DNA of lymphoid organs was severely damaged by the toxin. In vitro, T2 toxin induced severe damage to the DNA molecule with low concentrations (5 ng/ml culture) and for short exposure (2 h). In vivo, a moderate amount of DNA breaks was observed in splenic and thymic lymphocytes 3 h after administration of T2 toxin to mice (3 mg/kg). Reversibility occurred 24 h later under these conditions in vivo, indicating DNA repair. The results agree with the preferential cytotoxicity of T2 toxin for lymphoid cells. The relation between DNA damage, mutagenicity and carcinogenic properties of T2 toxin is discussed.