Normal human fibroblasts in vitro were used as a system to examine the cellular effects of potentially toxic compounds. In addition to tests for viability, indices of toxicity were included which would demonstrate functional and structural alterations associated with specific subcellular components. Fibroblast cultures derived from human neonatal foreskin were treated with various doses of the mycotoxins T-2 and T-2 tetraol. Methods for demonstrating viability showed T-2 to be 10-fold more toxic than its hydroxylated derivative, T-2 tetraol. Both compounds induced a dose-dependent reduction in protein and scheduled DNA synthesis, as well as an induction of unscheduled DNA synthesis (DNA repair). However, no qualitative alterations in the activity of cytoplasmic, lysosomal or membrane-associated enzymes were observed with T-2 or T-2 tetraol-treated cells. Transmission electron microscopy revealed structural alterations predominantly associated with the nucleus and the endoplasmic reticulum with associated ribosomes. Multiple biochemical parameters with ultrastructural and cytotoxicity studies were therefore effective in demonstrating the mechanisms as well as the degree of toxicity induced by these chemical compounds.
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