Synthesis of DNA in human fibroblasts treated with T-2 toxin and HT-2 toxin (the trichothecene metabolites of Fusarium species) and the effects of hydroxyurea.

(1) 3alpha-Hydroxy-4beta, 15-diacetoxy-8alpha-(3-methylbutyryloxy)-12,13-epoxytrichothec-9-ene (T-2 toxin) and HT-2 toxin both inhibited the incorporation of tritiated thymidine into the DNA of human fibroblasts; the inhibition was dose-related. (2) The presence of hydroxyurea (HU) did not affect unscheduled DNA synthesis in human fibroblasts damaged by T-2 toxin (0.006 mug/ml to 20.0 mug/ml) or by HT-2 toxin (0.032 mug/ml to 100.0 mug/ml) as with cycloheximide. (3) In the presence of the rat-liver microsomal fraction, S-9 and of hydroxyurea, there was an increase in unscheduled DNA synthesis in human fibroblasts exposed to 100 mug/ml of HT-2 toxin. (4) Thus in the presence of the microsomal S-9 fraction and of hydroxyurea the effect of HT-2 toxin (at 100 mug/ml) appeared to resemble that of benzo(a)pyrene: further studies are needed to clarify the ròle of its derivatives in the mechanism of action of T-2 toxin.