Abstract
The initial changes in rat liver after a single oral dose of 7,12-dimethylbenz[a]anthracene (DMBA) (100 mg/kg b.w.) were examined ultrastructually. Glycogen granules of centrilobular hepatocytes increased with time to peak on Day 1. After this, they sharply decreased on Day 2, and on Days 5-10 returned to levels similar to those of the vehicle group (corn oil). On Day 2, the size of the centrilobular hepatocytes was decreased significantly, and the nuclear to cytoplasmic ratio was increased significantly. While the activity of hepatic glycogen phosphorylase a was decreased at 6-12 hrs and on Day 1, on Days 2-10, it was elevated to a level similar to that of the vehicle group. Thus, the initial temporary storage of hepatic glycogen granules following DMBA administration involved the inhibition of glycogenolysis in centrilobular hepatocytes. Glycogen granules appeared in restricted regions near the smooth endoplasmic reticulum (sER). Following DMBA administration, proliferation of sER of the centrilobular hepatocytes also gradually increased with time to peak on Day 2, after which it decreased, and on Days 5-10 returned to a level similar to that of the vehicle group. Results from the present study indicate that exposure of rats to DMBA could induce a reversible initial change in the hepatic glycogen metabolism. Moreover, the glycogen depletion of hepatocytes might be related to the high proliferation of sER that occurred concurrently on Day 2.
