Liver Cell Specific Toxicity of Xenobiotics
Steinberg, P; Oesch, F
| HERO ID | 3004225 |
|---|---|
| Year | 1992 |
| Title | Liver Cell Specific Toxicity of Xenobiotics |
| Authors | Steinberg, P; Oesch, F |
| Volume | Specific Toxicity |
| Page Numbers | Biochemical Mechanisms |
| Abstract | The mechanisms underlying the liver cell specific toxicity of structurally diverse xenobiotics were discussed. Studies indicated that the distribution and activities of aminopyrine-N-demethylase, ethoxyresorufin-O-deethylase, microsomal epoxide-hydrolase, and cytosolic glutathione-transferase were not restricted to liver parenchymal cells, but were also located in Kupffer and endothelial cells. Morphological investigations in experimental animals revealed that peroxisomes were confined to liver parenchymal cells in untreated animals, but could be observed in endothelial cells of peroxisome proliferator treated animals. The ability of isolated liver Kupffer and endothelial cells to metabolically activate carcinogens into mutagenic metabolites was compared with that of liver parenchymal cells. Studies indicated that parenchymal, Kupffer, and liver endothelial cells were able to activate carcinogens into mutagenic metabolites. The ability of all three types of cells to metabolically activate these compounds may have been due to the amount of cytochrome-450 present in the cells. Several experiments elucidated the binding mechanism of aflatoxin-B1 (1162658), benzo(a)pyrene (50328), dimethylnitrosamine (4164287), 1,2-dimethylhydrazine (540738), and vinyl-chloride (75014) to DNA of liver parenchymal and nonparenchymal cells, and the genotoxic effects of these compounds. The authors conclude that although the parenchymal cell is primarily responsible for the activation of xenobiotic compounds in the liver, nonparenchymal cells such as Kupffer and endothelial cells possess cytochrome-450 enzyme activities which may be sufficient to activate several structurally different compounds. |
| Report Number | NIOSH/00211019 |
| Is Certified Translation | No |
| Dupe Override | 3004225 |
| Comments | Journal: Tissue ISSN: |
| Is Public | Yes |