The interaction of triethyl lead with tubulin and microtubules.
The impact of triethyl lead chloride was studied on: (i) the in vitro assembly and disassembly of microtubules from porcine brain by turbidometry and electron microscopy, (ii) the microtubule system of living mammalian cells using immunofluorescence microscopy, (iii) cell motility and chemotaxis employing the methods of phagokinetic track formation and the Boyden chamber assay, respectively, and (iv) thiol groups of the protein tubulin by their titration in the presence and absence of the organic lead compound. Triethyl lead chloride inhibited microtubule assembly and depolymerized preformed microtubules in vitro and in living cells. Random motility of cells was not markedly inhibited by triethyl lead chloride, whereas chemotaxis (directed cellular movement) was strongly inhibited. Triethyl lead chloride was found to interact with 2 thiol groups of the tubulin dimer. The interaction of triethyl lead chloride with the tubulin/microtubule system in vivo likely causes aneuploidy and is at least partly responsible for the cytotoxicity of the drug.
Zimmermann
H P
HP
Institute of Cell and Tumor Biology, German Cancer Research Center, Heidelberg.
Faulstich
H
H
Hänsch
G M
GM
Doenges
K H
KH
Stournaras
C
C
D000818:Animals; D001921:Brain / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D066298:In Vitro Techniques; D007854:Lead / Q000494:pharmacology*; D008870:Microtubules / Q000187:drug effects*; D009942:Organometallic Compounds / Q000494:pharmacology*; D013552:Swine; D014404:Tubulin / Q000096:biosynthesis*
D009942:Organometallic Compounds; D014404:Tubulin; D007854:Lead; C010360:triethyllead