Disturbed microtubule function and induction of micronuclei by chelate complexes of mercury(II).
Interactions of mercury(II) with the microtubule network of cells may lead to genotoxicity. Complexation of mercury(II) with EDTA is currently being discussed for its employment in detoxification processes of polluted sites. This prompted us to re-evaluate the effects of such complexing agents on certain aspects of mercury toxicity, by examining the influences of mercury(II) complexes on tubulin assembly and kinesin-driven motility of microtubules. The genotoxic effects were studied using the micronucleus assay in V79 Chinese hamster fibroblasts. Mercury(II) complexes with EDTA and related chelators interfered dose-dependently with tubulin assembly and microtubule motility in vitro. The no-effect-concentration for assembly inhibition was 1 microM of complexed Hg(II), and for inhibition of motility it was 0.05 microM, respectively. These findings are supported on the genotoxicity level by the results of the micronucleus assay, with micronuclei being induced dose-dependently starting at concentrations of about 0.05 microM of complexed Hg(II). Generally, the no-effect-concentrations for complexed mercury(II) found in the cell-free systems and in cellular assays (including the micronucleus test) were identical with or similar to results for mercury tested in the absence of chelators. This indicates that mercury(II) has a much higher affinity to sulfhydryls of cytoskeletal proteins than to this type of complexing agents. Therefore, the suitability of EDTA and related compounds for remediation of environmental mercury contamination or for other detoxification purposes involving mercury has to be questioned.
Stoiber
Thomas
T
Institut für Molekulare Biotechnologie, Beutenbergstr. 11, Jena D-07745, Germany. tstoiber@imb-jena.de
Bonacker
Daniela
D
Böhm
Konrad J
KJ
Bolt
Hermann M
HM
Thier
Ricarda
R
Degen
Gisela H
GH
Unger
Eberhard
E
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000633:toxicity*; D005455:Fluorescent Antibody Technique; D008628:Mercury / Q000378:metabolism / Q000633:toxicity*; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D008854:Microscopy, Electron; D008870:Microtubules / Q000187:drug effects*; D013552:Swine
D004492:Edetic Acid; D008628:Mercury