Interaction of triethyl lead chloride with microtubules in vitro and in mammalian cells.
The effects of triethyl lead chloride (TriEL) on the in vitro assembly and disassembly of microtubules (MTs) from porcine brain were studied by turbidometry at 350 nm and by electron microscopy. TriEL inhibited MT assembly at 50 microM concentration and caused an almost complete disassembly of preformed MTs. The drug depolymerized MTs more effectively than colchicine. Concentrations higher than 50 microM TriEL caused an aberrant assembly process. Fibers about 10 nm width were formed in addition to aggregates of amorphous material. In vivo TriEL also caused MT depolymerization in interphase and mitotic PtK-1 and Ehrlich ascites tumor (EAT) cells as monitored by indirect immuno-fluorescent staining of tubulin and electron microscopy. The extent of MT depolymerization was concentration- and time-dependent. Recovery occurred as early as 5 min after removal of the drug. The fluorescent actin pattern in PtK-1 cells typical of stress fibers and subcortical filaments seemed not to be altered by the presence of TriEL. The vimentin intermediate filament system was, however, rearranged as a juxtanuclear complex after TriEL treatment. Furthermore, TriEL effected the inhibition of cellular growth (100% inhibition at about 10(-5) M). Cytokinesis is prevented to a great extent, resulting in the formation of binucleate cells which can additionally possess some micronuclei.
D000818:Animals; D001921:Brain / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003078:Colchicine / Q000494:pharmacology; D004173:Dipodomys; D005455:Fluorescent Antibody Technique; D007700:Kinetics; D007854:Lead / Q000494:pharmacology*; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure*; D009498:Neurotoxins / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000494:pharmacology*; D013552:Swine; D014404:Tubulin / Q000302:isolation & purification
D009498:Neurotoxins; D009942:Organometallic Compounds; D014404:Tubulin; D007854:Lead; C010360:triethyllead; D003078:Colchicine