Hepatocarcinogenesis by thioacetamide: correlations of histological and biochemical changes, and possible role of cell injury.

Hepatocarcinogenesis in rats produced by prolonged feeding of thioacetamide appears as a progressive phenomenon in which morphological changes are associated with important biochemical modifications. It seems most likely that changes in the permeability of cell membrane induced by the carcinogen are responsible for increased intracellular accumulation of Ca2+, and for the ensuring of cell injury produced by Ca2+ overloading of the mitochondria. This calcification of the mitochondria may play a role in the neoplastic transformation of the cell, especially as far as it concerns metabolic behavior and the genetic specification of the permeability characteristics of the transformed cell membrane. The increased synthesis of acid glycosaminoglycans suggests their involvement in calcium-mediated control of tumor development and growth.