Immunohistochemical localization of trichloroacylated protein adducts in tetrachloroethene-treated mice.
Tetrachloroethene (PCE), a common industrial solvent and environmental contaminant, is primarily used in the dry-cleaning industry. The toxicity of PCE has been linked to vision disorders, renal and hepatic cancer, and autoimmune diseases. Although the mechanism of toxicity is not fully understood, PCE forms trichloroacylated protein adducts in tissues where toxicity is known to occur. These adducts may be responsible for toxicity by altering the function of cellular proteins. Using Western blot analysis, formation of trichloroacylated protein adducts has been reported. To determine the localization of the adducts in a specific zone of a tissue, immunohistochemical staining was used in the study. An antiserum to trichloroacylated proteins was raised in rabbits and its specificity was established by enzyme-linked immunosorbent assay (ELISA). Female MRL-lpr/lpr and MRL +/+ mice were treated with PCE using a single 5-mmol/kg dose over 24 h or on every fourth day for 6 wk (total 20 doses). Formation of trichloroacylated protein adducts was observed in the liver, and localized to the centrilobular zones. Intensity and circumference of the staining around the central vein were much greater in subchronically treated mice than in acutely treated mice. No immunochemical reactivity was observed in any of the other tissues examined. This study shows that hepatic trichloroacylated protein adducts are localized in a region of the liver where PCE-mediated toxicity is known to occur. Immunohistochemical localization of these adducts and its association with PCE-induced toxicity support the contention that adducts may contribute to toxicity.
Green
S M
SM
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555-0609, USA.
Khan
M F
MF
Kaphalia
B S
BS
Ansari
G A
GA
D000215:Acylation; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D019463:Mice, Inbred MRL lpr; D011485:Protein Binding; D011897:Random Allocation; D012997:Solvents / Q000378:metabolism / Q000633:toxicity*; D013750:Tetrachloroethylene / Q000378:metabolism / Q000633:toxicity*; D014018:Tissue Distribution
D012997:Solvents; D013750:Tetrachloroethylene