Occurrence of cell death (apoptosis) during the involution of liver hyperplasia.

A single intravenous injection of lead nitrate at a dose of 10 mumoles/100 gm of body weight caused liver enlargement associated with hepatic cell proliferation. In the present study the involution of liver hyperplasia which follows the withdrawal of lead was studied in male Wistar rats. Histologic examination of liver sections from rats killed during the regression of the liver did not show any sign of massive lytic cell necrosis; no variation in the levels of serum glutamate pyruvate transaminase could be observed during the same time period; however, light microscopic observation of sections from the involuting liver showed the presence of several apoptotic bodies; the occurrence of apoptotic bodies was also confirmed by ultrastructural examination. Their incidence was found to be markedly increased at 5 days after treatment, a time period when the liver is already regressing; very few apoptotic bodies were observed in control animals or in treated rats 2 days after lead injection, a time point when mitotic index reached its maximum, or at 15 days, when the liver had returned to control values. These findings suggest that removal of excess liver which follows the initial hyperplasia caused by lead is due to a controlled mode of cell death, namely, apoptosis.