Long-term evolution of the main changes induced by thioacetamide on hepatocytes

The results of an electron microscopic study of the changes in hepatocytes induced by chronic intoxication with thioacetamide are reported. During the poisoning aspecific toxic changes are intermingled with progressive, preneoplastic ones. The main cell subpopulations identified are: 1) large hepatocytes with smooth endoplasmic reticulum (SER) hypertrophy, with or without rough endoplasmic reticulum (RER) neoformation and glycogen storage, which is starvation resistant; 2) smaller hepatocytes, where RER hypertrophy and ribosome accumulation are the prominent features. Such a pattern persists for months. After the withdrawal of the drug most of the cell changes disappear. However, during this time a simplification of the liver structure and cell composition takes place, allowing a sequence of cell events which seem relevant for establishment of neoplastic progression. The SER-hypertrophied cell appears first and gives rise, via several intermediate stages, to the RER-hypertrophied one, which is believed to play a key role as the ultimate precursor of cancer cells.