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Interaction of metal salts with cytoskeletal motor protein systems
R Thier1, D Bonacker, T Stoiber
1School of Biomedical Sciences, University of Queensland, Qld 4072, St. Lucia, Australia. r.thier@uq.edu.au
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 microM PbCl(2), 0.05 microM Pb(OAc)(2) and 0.01 microM HgCl(2). The in vitro results obtained for PbCl(2) correspond to reported MN induction in workers occupationally exposed to lead, starting at 1.2 microM 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 microM. Inhibition of tubulin assembly by mercury started at 2 microM. The gliding velocity of microtubules along immobilised kinesin molecules was affected by 25 microM Pb(NO(3))(2) and 0.1 microM HgCl(2) 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.
Insights
Lead and mercury salts induce genotoxicity by interfering with cellular microtubule networks. These metals disrupt tubulin assembly and motor protein function, potentially leading to chromosome segregation errors and micronuclei formation.
Area of Science:
- Toxicology
- Cell Biology
- Genetics
Background:
- Chemicals interacting with the microtubular network can cause genotoxicity.
- Metals like lead and mercury may induce micronuclei by affecting tubulin and kinesin.
Purpose of the Study:
- To investigate the genotoxic effects of inorganic lead and mercury salts.
- To examine the impact of these metals on cytoskeletal protein function.
Main Methods:
- Micronucleus (MN) assay and CREST analysis in V79 Chinese hamster fibroblasts.
- In vitro measurement of tubulin assembly and kinesin-driven motility.
Main Results:
- Lead and mercury salts induced micronuclei formation in a dose-dependent manner.
- Both metals interfered with tubulin assembly, while lead and mercury also affected kinesin-driven microtubule motility.
- CREST analysis indicated aneugenic effects for lead and both aneugenic and clastogenic effects for mercury.
Conclusions:
- Lead and mercury genotoxicity may stem from disruptions in chromosome segregation due to interactions with cytoskeletal proteins.
- The study supports the hypothesis that metal-induced genotoxicity involves interference with microtubule dynamics.