Interaction of metal salts with cytoskeletal motor protein systems.
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.
Thier
R
R
School of Biomedical Sciences, University of Queensland, Qld 4072, St. Lucia, Australia. r.thier@uq.edu.au
Bonacker
D
D
Stoiber
T
T
Böhm
K J
KJ
Wang
M
M
Unger
E
E
Bolt
H M
HM
Degen
G
G
D000818:Animals; D006224:Cricetinae; D003599:Cytoskeleton / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007854:Lead / Q000633:toxicity*; D017669:Mercury Compounds / Q000633:toxicity*; D015162:Micronucleus Tests / Q000379:methods; D009152:Mutagenicity Tests; D009942:Organometallic Compounds / Q000633:toxicity*; D014404:Tubulin / Q000187:drug effects*
D017669:Mercury Compounds; D009942:Organometallic Compounds; D014404:Tubulin; D007854:Lead; C029891:lead chloride; C008261:lead acetate