p-Hydroxypropiophenone Effects on Azo Dye-Induced Alterations in Mouse Hepatic Cells: Light and Electron Microscopic Study

Summary

The progressive changes produced in hepatocytes after long-term exposure of mice to the carcinogen dimethylaminoazobenzene (DAB) were studied. p-Hydroxypropiophenone (PHP), an inhibitor of DAB-induced hepatoma in rats, was used to determine whether similar inhibitory effects occurred in mice. After 3 weeks of DAB administration, light microscopy revealed a disruption of hepatic cords and hepatocytes with clear cytoplasm after hematoxylin and eosin staining and a less than normal reaction for glycogen after periodic acid-Schiff staining. After 9 weeks, several small nodules were observable. Some of the prominent ultrastructural alterations in liver cells after 3 weeks of DAB feeding were: increase in the branching tubular network of smooth endoplasmic reticulum, increase in the number of free ribosomes, disorganization and apparent reduction in rough endoplasmic reticulum profiles, increase in electron density of mitochondrial matrix, peripheralization of chromatin material, and partial segregation of nucleolar content. These changes were accentuated at 6–9 weeks of DAB feeding, but the number of cells with them decreased on prolonged DAB administration; moreover, these alterations were less severe in altered cells. Since cells of mice fed DAB plus PHP exhibited only slight initial changes after 3 weeks/PHP apparently inhibits DAB-induced alterations in mouse liver cells, but its mode of action is not yet understood.