Ultrastructural effects of T-2 mycotoxin on rat hepatocytes in vitro

Cultured rat hepatocytes were treated with several doses of T-2 mycotoxin for either 1 or 12 hr and with or without a 12 hr recovery period. Inhibition of protein synthesis and release of lactate dehydrogenase were measured and correlated with ultrastructural changes, as assessed by transmission electron microscopy. Results indicated that at a dose of 0.01 microgram/ml protein synthesis was inhibited 75% within 1 hr, but recovered to near control levels with or without the continual presence of toxin. At the higher toxin dose of 1.0 microgram/ml hepatocytes were able to recover from a 1 hr, but not a 12 hr, exposure. Cell damage, as assessed by release of lactate dehydrogenase, lagged behind inhibition of protein synthesis. Only at a T-2 concentration of 1.0 microgram/ml for 12 hr followed by a 12 hr recovery period was release of lactate dehydrogenase significantly elevated over control values. Under the same parameters, protein synthesis was inhibited 94%. The ultrastructural appearance of the cell membrane, nucleus, lysosomes, peroxisomes and smooth endoplasmic reticulum remained unchanged. The two organelles which appeared altered by T-2 exposure were the rough endoplasmic reticulum and the mitochondria. Endoplasmic reticulum changes were limited to degranulation of attached ribosomes without dilation of the cisternae. Alterations were seen as early as 1 hr at a T-2 dose of 0.01 microgram/ml. After a dose of 1.0 microgram/ml T-2 for 12 hr some mitochondria displayed one or more non-membrane-bound translucent foci, some of which contained electron-dense cores.