Interaction of metal salts with cytoskeletal motor protein systems

Thier, R., Bonacker, D., Stoiber, T., Böhm, K. J., Wang, M., Unger, E., Bolt, H. M., & Degen, G. (2003) Interaction of metal salts with cytoskeletal motor protein systems. Toxicology Letters, 140-141, pp. 75-81.

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Abstract

Interactions of chemicals with the microtubular network of cells may lead to genotoxicity. Micronuclei (MN) might be caused by interaction of metals with tubulin and/or kinesin. The genotoxic effects of inorganic lead and mercury salts were studied using the MN assay and the CREST analysis in V79 Chinese hamster fibroblasts. Effects on the functional activity of motor protein systems were examined by measurement of tubulin assembly and kinesin-driven motility. Lead and mercury salts induced MN dose-dependently. The no-effect-concentration for MN induction was 1.1 μM PbCl2, 0.05 μM Pb(OAc)2 and 0.01 μM HgCl2. The in vitro results obtained for PbCl2 correspond to reported MN induction in workers occupationally exposed to lead, starting at 1.2 μM Hg(II) (Vaglenov et al., 2001, Environ. Health Perspect. 109, 295-298). The CREST Analysis indicate aneugenic effects of Pb(II) and aneugenic and additionally clastogenic effects of Hg(II). Lead (chloride, acetate, and nitrate) and mercury (chloride and nitrate) interfered dose-dependently with tubulin assembly in vitro. The no-effect-concentration for lead salts in this assay was 10 μM. Inhibition of tubulin assembly by mercury started at 2 μM. The gliding velocity of microtubules along immobilised kinesin molecules was affected by 25 μM Pb(NO3)2 and 0.1 μM HgCl2 in a dose-dependent manner. Our data support the hypothesis that lead and mercury genotoxicity may result, at least in part, via disturbance of chromosome segregation via interaction with cytoskeletal proteins.

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ID Code: 77479
Item Type: Journal Article
Refereed: Yes
Additional Information: Proceedings of EUROTOX 2002, The XL European Congress of Toxicology. Budapest, Hungary. 15–18 September 2002
Keywords: Cytoskeletal motor protein, Genotoxicity, Lead, Mercury, Micronucleus test, Tubulin, aneugen, clastogen, cytoskeleton protein, kinesin, lead acetate, lead chloride, lead nitrate, mercuric nitrate, mercury chloride, metal complex, animal cell, Chinese hamster, chromosome segregation, conference paper, controlled study, dose response, fibroblast, micronucleus, microtubule organizing center, nonhuman, priority journal, protein interaction, protein transport, Animals, Cricetinae, Cytoskeleton, Dose-Response Relationship, Drug, Mercury Compounds, Micronucleus Tests, Mutagenicity Tests, Organometallic Compounds, Cricetulus griseus
DOI: 10.1016/S0378-4274(02)00502-7
ISSN: 0378-4274
Divisions: Current > Schools > School of Clinical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Copyright Owner: Copyright 2003 Elsevier Science Ireland Ltd.
Deposited On: 15 Oct 2014 23:51
Last Modified: 17 Oct 2014 03:19

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