Regulation of cell turnover in the liver of tumour-bearing rats: occurrence of apoptosis

Growth of a highly‐deviated ascites hepatoma (Yoshida AH‐130) in rats caused initial hyperplastic enlargement of the liver, followed by progressive reduction to a size lower than that seen in controls. The time‐course of this biphasic change in liver weight roughly corresponded to the exponential and stationary phases of tumour growth. Histologically, scattered small foci of perilobular necrosis were observed during the hyperplastic phase and these were consistently associated with a moderate elevation of glutamate‐pyruvate transaminase (GPT) activity in the blood plasma. By contrast, signs of necrosis were absent and plasma GTP levels had returned to normal during the phase of hepatic involution, which was characterized by enhanced apoptosis, a type of single‐cell death known to be involved in the regulation of tissue size under both normal and pathological conditions. Biochemically, alterations in liver protein mass resulted from changed rates of tissue protein degradation. The apoptotic bodies could either be lost from the liver via blood, lymph and bile, or phagocytosed and degraded by adjacent cells. Disposal of the apoptotic bodies is likely to account, at least in part, for the enhanced rates of liver protein turnover that characterize hepatic involution.