Acute and persistent ultrastructural changes in rat liver after a single dose of 2-acetylaminofluorene: effect of co-administration of cycloheximide.

Electron microscope studies have been made of rat hepatic cell morphology, 24 hr, 48 hr and 24 weeks after a single intragastric dose of 2-acetylaminofluorene (2-AFF), alone or together with a single s.c. dose of cycloheximide (CHM). CHM prevents the acute perinuclear glycogen pooling, peripheral displacement of cytoplasmic organelles and nuclear shrinkage induced by 2-AAF. However, the induction by 2-AAF of changes in the granular endoplasmic reticulum, mitochondria and bile canaliculi is enhanced by co-administration of CHM. These changes persist for at least 24 weeks and are similar to those induced during 2-AAF hepatocarcinogenesis and observed in hepatocellular tumours. In view of the similar results obtained in previous studies with the azocarcinogen, 3'-methyl-4-dimethylaminoazobenzene, the possibility is discussed that these persistent changes might be associated with the initiation phase of neoplastic induction.