Fixation of the plasma membrane/cytoplasm complex: a mechanism of toxic interaction of tributyltin with the cell.
Flow cytometric and light/fluorescence microscopic analysis of murine erythroleukemic cells (MELC) and electron microscopic investigation of porcine microsomal membrane preparations suggest that tributyltin (TBT) toxicity is mediated through fixation processes (protein denaturation, crosslinking, and so on) within the plasma membrane/cytoplasm complex. This hypothesis was derived from the following observations: 1. Exposure of the MELC to micromolar concentrations of TBT results in increased resistance to detergent-mediated cytolysis; 2. Exposure of porcine renal microsomal membrane preparations to similar concentrations results in inhibition of vanadate-mediated crystallization of Na+,K(+)-ATPase, a process requiring protein mobility within the membrane; 3. Flow cytometric and fluorescence microscopic analyses indicate that MELC exposed to submicromolar concentrations of TBT exhibit increased cellular carboxyfluorescein retention; and 4. Nuclei prepared from TBT-treated cells by detergent-mediated cytolysis exhibit increased axial light loss, 90 degrees light scatter, fluorescein isothiocyanate fluorescence, and the presence of adherent proteinaceous tags. The DNA distribution histogram of such nuclei also is perturbed.
Massaro
E J
EJ
Developmental and Cell Toxicology Division, US Environmental Protection Agency, Research Triangle Park, NC 27711.
Zucker
R M
RM
Elstein
K H
KH
Ting-Beall
H P
HP
Easterling
R E
RE
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure*; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D003460:Crystallization; D003593:Cytoplasm / Q000187:drug effects / Q000648:ultrastructure*; D000431:Ethanol; D005452:Fluoresceins; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology; D011489:Protein Denaturation; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013194:Staining and Labeling; D013552:Swine; D014220:Trialkyltin Compounds / Q000633:toxicity*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D005452:Fluoresceins; D014220:Trialkyltin Compounds; C024098:6-carboxyfluorescein; D000431:Ethanol; C011559:tributyltin; D000254:Sodium-Potassium-Exchanging ATPase