Ultrastructural study of rat liver and liver neoplasms after long-term treatment with phenobarbital

The purpose of this investigation is to study the ultrastructure of liver and liver neoplasms after long-term administration of phenobarbital. Liver from female Charles River rats treated with 0.1% sodium phenobarbital by dietary admix for 60, 180, or 113 weeks was examined; liver neoplasms present at 108 or 113 weeks were also examined. At 60 weeks, an outstanding feature of most hepatocytes was the extensive proliferation of smooth endoplasmic reticulum, increase in autophage vacuoles, lysosomes, blebbing, and Kupffer cells containing phagosomes. At 108 or 113 weeks, additional changes in liver included an abundance of myelin figures in vacuoles, sinusoids, and bile canaliculi and the occasional appearance of whorls of smooth endoplasmic reticulum. Hepatocytes from liver neoplasms, all identified as well-differentiated hepatic cell neoplasms, contained voluminous whorls and large phagosomes filled with whorls, myelin figures, and cellular debris. The phagosomes were present both intracytoplasmic and intrasinusoidal, either partially or completely surrounded by Kupffer cell extensions. These cellular alterations are interpreted as evidence of adaptive cellular responses.