The Effect of Thioacetamide on Rat Liver Regeneration

Partial hepatectomy initiates a complex pattern of cellular changes in the parenchymal cells of the residual liver. The sudden shift of the cell population from normal functional biosyntheses toward syntheses in preparation for cell division provides an ideal system for the study of various aspects of cell metabolism. The morphological and biochemical changes associated with liver restoration have been described and reviewed by many investigators (1, 14, ~ , ~6, 87). The earliest changes noted are the conspicuous nucleoli and a cytoplasm rich in ribonucleic acid, a pattern typical of cells engaged in increased or altered protein synthesis. I t is now generally accepted tha t nucleic acids are intimately involved in cellular growth and biosyntheses. Ribonucleic acid (RNA) changes are correlated with the variations in the rate of protein synthesis, while deoxyribonucleic acid (DNA) is associated with mitotic activity (reviews, 5, 43, 47). Previous studies have shown that thioacetamide (CH3CSNH~) induces cellular changes in rat liver similar in some respects to those occurring after partial hepatectomy (39). The most striking effect is the increase in nuclear ribonucleoprotein (~9, 31). The nucleoli increase to gigantic proportions, and nuclear RNA synthesis is greatly accelerated.1 Drug treatment by injection (31) or feeding for 10 weeks (~0) does not impair regeneration after partial hepatectomy. I t was felt that thioacetamide (TA)-treated animals would provide a useful system for studying the effect of increased nuclear RNA on growing and dividing cells. TA-treated rats were subjected to partial hepatectomy and some of the general aspects of restorative growth analyzed, i.e., rate of regeneration, volume