Detection of adenovirus and initiation of apoptosis in hepatocellular carcinoma cells after Ad-p53 treatment.
Transcription of the p53 gene can regulate progression of apoptosis in a wide variety of tissues. Three categories of human hepatocyte culture have been used to show the initiation of apoptosis after treatment with p53-bearing adenovirus. Chang liver cells are derived from normal liver tissue and express native p53, whereas hepatocellular carcinoma (HCC)-derived cell lines were Hep3B (p53-deleted) and PLC/PRF/5 (p53-mutant). Cultures were infected with Ad-p53 (15 particles per cell; 36 hours), and after treatment, morphological changes in all cell categories were observed by electron microscopy. Infection was evident in the cytoplasm of all treated cell types: after entry across the plasma membrane viruses translocated and came to rest surrounding and adjacent to nuclei, cytoplasm proximal to nuclear membranes became dense with virus- and membrane-derived debris, but intact viruses did not enter nuclei. Apoptosis, recognized morphologically by characteristic chromatin and cytoplasmic condensation, occurred more frequently in HCC-derived cells, and the ultimate fate of apoptotic bodies was phagocytosis and degradation by neighboring cells.
Mitry
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RR
Liver Surgery Section, Imperial College School of Medicine, Hammersmith Hospital Campus, London, UK.
Sarraf
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CE
Havlík
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R
Habib
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NA
D000256:Adenoviridae / Q000235:genetics*; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology*; D002467:Cell Nucleus / Q000648:ultrastructure; D002843:Chromatin / Q000648:ultrastructure; D003593:Cytoplasm / Q000648:ultrastructure; D017353:Gene Deletion; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology*; D008854:Microscopy, Electron; D009154:Mutation; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D002843:Chromatin; D016159:Tumor Suppressor Protein p53