Ultrastructural and Autoradiographic Studies of the Effect of Aflatoxin G1 on Hepatic Cells

ABSTRACT

To investigate toxicity of aflatoxin Gl and its mechanism, light microscopic, histochemical, electron microscopic and autoradiographic studies were done on the rat liver at various time intervals after the administration of aflatoxin Gl. Light microscopic alteration was first observed at 6 hours and necrosis of periportal hepatic cells was found at 18 hours. However, reduction of Feulgen positivity of the nucleus and pyroninophilia of cytoplasm was observed as early as 1 hour. Ultrastructural changes were noted at 6 hours and were advanced at l8 hours. Early changes consisted of nucleolar segregation, dilatation of rough endoplasmic reticulum, swelling of mitochondria and detachment of membrane bound ribosomes followed later by disruption of cytoplasmic organellae and focal necrosis. These changes were most marked at periportal region. Autoradiographic studies showed inhibition of H3-uridine incorporation into the nucleus at 1 hour, was most marked at 6 hours, and showed some recovery at 18 hours. H3-uridine labeling in the cytoplasm was also inhibited and the most marked inhibition was noted at 1 hour after the aflatoxin administration. These data indicate aflatoxin Gi has a hepatotoxic effect, particulary at the periportal region. This toxic effect is likely due to inhibition of nuclear RNA synthesis which leads to inhibition of ribosomal RNA and eventually protein synthesis. The DNA synthesis is also inhibited, as shown by reduction of Feulgen reaction in the nucleus.