Apoptosis and cell proliferation in rat hepatocytes induced by barbiturates

To examine the effect on cell population in hepatocytes of phenobarbital (P B) and other barbiturates, PB, allobarbital (ALB), barbital sodium (BS) and barbituric acid (BA) were given orally to male rats for 7 consecutive days . Although there was no apparent change in non-promoting BA, hepatomegaly w as induced by PB, BS and ALB, which are promoters of hepatocarcinogenesis. In PB- and BS-treated livers, hepatomegaly was attributable to hepatocyte p roliferation and enzyme induction. In ALB-treated liver, it was attributabl e to enzyme induction. The level of cell proliferation was reduced to less than the control values following withdrawal of PB, ALB and BS. It seemed t hat the degree of suppression of cell proliferation following withdrawal of these compounds correlated to the degree of cell proliferation (PB>BS>ALB) during treatment. In PB-treated liver, apoptosis was induced during treatm ent, serving to eliminate the excess of hepatocytes. This suggests that sho rt-term administration of PB neither induced suppression of apoptosis nor d isturbed homeostasis of hepatocyte populations.