[Effect of aflatoxin B1 on ultrastructural changes of biliary epithelial cells in mice experimentally infected with...

The present study was carried out to examine the effect of a carcinogen, aflatoxin B1 on the ultrastructural changes of biliary epithelial cells in mice infected with Clonorchis sinensis. A total of 93 male albino mice(BALB/c strain) was divided into 3 groups; group I, treated with 1.0 ppm aflatoxin B1 for 12 weeks; group II, given 50 C. sinensis metacercariae, and group III, given 50 metacercariae and treated with 1.0 ppm aflatoxin B1 for 12 weeks. Three mice served for untreated-uninfected controls. From 4 weeks after the treatment and/or infection, three mice from each group were sacrificed at 4 week intervals up to the 40th week, and their hepatobiliary tissues were prepared for transmission electron microscopy. The most prominent ultrastructural changes in group I were remarkable enlargement of nuclear size, separation of nucleolus, dispersed chromatin granules in nuclei and increased dense granules along the inner membrane of nuclei. In the cytoplasm there was slight proliferation of mitochondria and endoplasmic reticulum (ER) at earlier stage. At the 12th week separation of fibrillar and granular components of the nucleolus was a characteristic finding. As the time elapsed, epithelial cells showed flattened-cuboidal form and a tendency of atrophy. Most of the nuclei were elongated and polygonal in shape. In group II the appearance of elaborate interwoven folds of lateral cytoplasm forming a labyrinth of interconnected intercellular space and variety in nuclear shape were the prominent findings at earlier stage. The cytoplasm showed slight proliferation and dilatation of mitochondria and ER, and a small number of mucin droplets. In the basement membrane scanty fibrous cells were seen. With time, variety in nuclear shape, marked proliferation and dilatation of rough ER and some collagen fibrils were demonstrated. Other features of intracellular organelles and mucin droplets persisted. In group III cuboidal epithelial cells showed their remarkably enlarged and irregular nuclei, increased chromatin granules in the nuclei, separated nucleoli, proliferated and dilated rough ER. With time, sequestered mitochondria showed bleb-like evaginations which lacked cristae and dense matrix, and were limited by a single membrane. Since the 20th week, microvilli were relatively scanty and poorly developed. Organelles and inclusions in the cytoplasm of metaplastic cells were poor. Nuclei were variable in shape. The most prominent changes at later stage were separation of nuclei from the cytoplasm, and appearance of numerous and irregularly angled electron dense granules in the nuclei.