Morphological alterations and focal deficiency of the histochemical activity of acid and alkaline nucleases in rat liver after chronic administration of phenobarbital

Chronic oral administration of phenobarbital (up to 16 months) did not produce any neoplastic foci or nodules in the liver of male Wistar rats. Decrease of glycogen content and cytoplasmic alterations probably indicating S.E.R. hypertrophy were observed in the hepatocytes localized predominantly in the centrilobular areas of rats after chronic phenobarbital treatment. This treatment induced small foci of alkaline DNAse and RNAse deficient liver cells in the initial stages of the experiment. Acid DNAse and RNAse deficient zones increased in liver parenchyma since the third month of chronic administration of phenobarbital. At later stages of the experiment (7 to 16 months) they concerned in some cases more than 50% of liver parenchyma. The hyperbasophilia and the intensity of methylgreen-pyronin staining which, most probably, indicated the accumulation of nucleic acids also increased progressively with phenobarbital administration in similarly distributed irregular zones. These zones had predominant centrilobular localization.

It was suggested that such zonal deficiency of acid nuclease activity might be involved in tumor-promoting action of phenobarbital when separately administered in rats after hepatocarcinogen treatment.