Hydrophobic interaction of organic chemicals with microtubule assembly in vitro.
A recent concept connecting the lipophilicity of organic chemicals with their genotoxicity on a chromosomal level implies that the lipophilic character of organic chemicals determines a certain background of chromosomal genotoxicity that can be addressed as "non-specific". This is opposed to compounds with more "specific" modes of action. Such mechanisms influence the processes of karyokinesis and cytokinesis. A critical partial process for the chromosomal segregation is the dynamics of assembly and disassembly of microtubules. To broaden the present database for such interactions, chemicals were selected based on their lipophilicity (log P between -1.5 and +1.0) and on hints from the literature pointing to possibilities of interaction with the tubulin-microtubule system. Thus, acetamide, acrylamide, methylmethane sulfonate, acetonitrile, acrylonitrile and cyclohexanone were assessed as to their potencies to influence the dynamic processes of microtubule assembly and disassembly in a cell-free system in vitro. These compounds covered a range of log P between -1.5 and 1.0, complementary to compounds investigated earlier. The entire body of data supports the general concept that hydrophobic interactions are connected with non-specific processes, which contribute to a background genotoxicity on a chromosomal level. It also points to the dynamics of microtubule assembly and disassembly as a decisive partial process involved.
Stoiber
Thomas
T
Leibniz Institute for Age Research, Fritz Lipmann Institute, Beutenbergstrasse 11, Jena, Germany.
Unger
Eberhard
E
Dorn
Susanne B
SB
Degen
Gisela H
GH
Bolt
Hermann M
HM
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D008055:Lipids / Q000737:chemistry; D008868:Microtubule Proteins / Q000096:biosynthesis; D008870:Microtubules / Q000187:drug effects / Q000502:physiology*; D009391:Nephelometry and Turbidimetry; D009930:Organic Chemicals / Q000737:chemistry* / Q000494:pharmacology*; D013552:Swine
D008055:Lipids; D008868:Microtubule Proteins; D009930:Organic Chemicals