Evaluation of Potential Exposure to Metals in Laundered Shop Towels

We reported in 2003 that exposure to metals on laundered shop towels (LSTs) could exceed toxicity criteria. New data from LSTs used by workers in North America document the continued presence of metals in freshly laundered towels. We assessed potential exposure to metals based on concentrations of metals on the LSTs, estimates of LST usage by employees, and the transfer of metals from LST-to-hand, hand-to-mouth, and LST-to-lip, under average- or high-exposure scenarios. Exposure estimates were compared to toxicity criteria. Under an average-exposure scenario (excluding metals’ data outliers), exceedances of the California Environmental Protection Agency, U.S. Environmental Protection Agency, and the Agency for Toxic Substances and Disease Registry toxicity criteria may occur for aluminum, cadmium, cobalt, copper, iron, and lead. Calculated intakes for these metals were up to more than 400-fold higher (lead) than their respective toxicity criterion. For the high-exposure scenario, additional exceedances may occur, and high-exposure intakes were up to 1,170-fold higher (lead) than their respective toxicity criterion. A sensitivity analysis indicated that alternate plausible assumptions could increase or decrease the magnitude of exceedances, but were unlikely to eliminate certain exceedances, particularly for lead.     

Microelements in seminal plasma of infertile men infected with Ureaplasma urealyticum

The purpose of this study was to assess the association among male infertility, infection of Ureaplasma urealyticum (Uu), and microelements in seminal fluid. Semen analysis and cultivation of Uu were carried out on 160 samples of seminal fluid. The concentrations of microelements, such as arsenic (As), molybdenum (Mo), magnesium (Mg), lead (Pb), copper (Cu), cadmium (Cd), and zinc (Zn) in the samples were measured by an inductively coupled plasma quantometer (ICP). The ratios Cu/Zn and Cd/Zn in the poor spermatic quality group were obviously higher than those in seminal plasma of the group with normal spermatic quality (p<0.01 and p<0.05, respectively), whereas the concentrations of As, Mg, Mo, and Pb showed no difference in the two groups. The ratios Cu/Zn and Cd/Zn and the concentrations of As and Mg in seminal plasma infected with Uu were markedly higher than those not infected with Uu (p<0.05, p<0.01, p<0.05, and p<0.05, respectively), whereas the concentrations of Mo and Pb showed no statistical difference. The ratios Cu/Zn and Cd/Zn and the concentrations of As and Mg in seminal plasma of the semen with poor spermatic quality and Uu infection were obviously higher than those not infected with Uu (p<0.05), whereas the concentrations of Mo and Pb showed no statistical difference. Abnormally high ratios Cu/Zn and Cd/Zn as well as an overdose of As were found to be predisposed to Uu infection. Uu infection resulted in an increase of the ratios Cu/Zn and Cd/Zn and the concentrations of As and Mg in seminal fluid, which therefore caused spermatic quality decline.     

Effects of Toxic Environmental Contaminants on Voltage-Gated Calcium Channel Function: From Past to Present

Voltage-gated Ca2+ channels are targets of the number of naturally occurring toxins, therapeutic agents as well as environmental toxicants. Because of similarities of their chemical structure to Ca2+ in terms of hydrated ionic radius, electron orbital configuration, or other chemical properties, polyvalent cations from aluminum to zinc variously interact with multiple types of voltage-gated Ca2+ channels. These nonphysiological metals have been used to study the structure and function of the Ca2+ channel, especially its permeability characteristics. Two nonphysiological cations, Pb2+ and Hg2+, as well as their organic derivatives, are environmental neurotoxicants which are highly potent Ca2+ channel blockers. These metals also apparently gain intracellular access in part by permeating through Ca2+ channels. In this review the history of Ca2+ channel block produced by Pb2+ and Hg2+ as well as other nonphysiological cations is traced. In particular the characteristics of Ca2+ channel block induced by these environmental neurotoxic metals and the consequences of this action for neuronal function are discussed.     

Characterization of cadmium- and lead- phytochelatin complexes formed in a marine microalga in response to metal exposure

Phytochelatins (PC_n) are thiol-containing peptides with general structure (-Glu-Cys)_n-Gly enzymatically synthesized by plants and algae in response to metal exposure. They are involved in the cellular detoxification mechanism for their capability to form stable metal-phytochelatin complexes. The speciation of Cd and Pb complexes with phytochelatins has been studied in laboratory cultures of the marine diatom Phaeodactylum tricornutum. An approach based on size-exclusion chromatography (SEC) with off-line detection of phytochelatins, by reverse-phase HPLC, and metal ion, by atomic absorption spectrometry, has been used. The formation of Cd- and Pb-PC_n complexes with n-value from 3 to 6 was demonstrated. The metal-PC_n complexes formed with Cd appear to be different from those formed with Pb for the number of molecules of peptide involved in the complex and for the amount of the metal ion bound. The chromatographic behaviour of metal-PC_n complexes is consistent with Pb-PC_n complexes in which only a molecule of peptide binds the metal ion, and with Cd-PC_n complexes containing two or more molecules of peptide. The metal/peptide molar ratio in Cd-PC_n complexes was higher that in Pb-PC_n complexes. The formation of Cd- or Pb-PC₂ complexes was not demonstrated, probably for a dissociation during the cellular extract preparation. The effectiveness of phytochelatins in the detoxification of these two metal ions in this alga is discussed.     

Optimalization of the peroxidase production by tissue cultures of horseradish <Emphasis Type="Italic">in vitro</Emphasis>

Tissue cultures of Armoracia rusticana L., both transformed with Agrobacterium rhizogenes and nontransformed, were screened for peroxidase activity. Most of the derived and tested strains exhibited 20 times higher activity [from 99 to 723 U g⁻¹(d.m.)] than the root of the intact plant [(30 U g⁻¹ (d.m.)]. The highest peroxidase activity was found in tumour culture growing on the medium without growth regulators. The influence of the addition of sugars and heavy metal ions in the medium on peroxidase production was tested. Increase in peroxidase activity was observed after cultivation of horseradish culture with cadmium, cobalt, nickel or lead ions.This work is supported by Grant Agency of Czech Republic Project No. 526/04/0135.     

Metal concentrations in the liver and kidney of aquatic mammals and penguins

We determined the hepatic and renal concentrations of Cd, Pb, Zn, Cu, and Fe in (1) marine mammals (three bottle-nosed dolphins, six California sea lions, and one sea otter), (2) freshwater and brackish-water mammals (one Oriental short-clawed otter and four European river otters), and (3) sea birds (three rock-hopper penguins, two king penguins, three Humboldt penguins, four Macaroni penguins, and four Magellanic penguins), all of which were kept in a zoo and an aquarium in Japan. We investigated the species-specificity of Cd accumulation in these aquatic animals. We also presented the basic data on metal concentrations. The concentrations of Cd in liver and kidney tended to be higher in marine mammals than in freshwater mammals. Many penguins, sea birds, showed high Cd concentrations. These results suggest that the habits of these animal species may be involved in accumulation of Cd. Pb concentrations were below the detection limit or low in both liver and kidney [not detected (ND)=0.132 μg/g and ND=0.183 μg/g, respectively]. The hepatic concentrations of Zn and Cu were high in young animals. In penguins, a positive correlation was found between the Zn and Cd concentrations in the liver and kidney and between the Cu and Cd concentrations in the liver. Individual variation was large in Fe concentration (48–3746 μg/g in the liver and 51–980 μg/g in the kidney).     

Zinc and lead uptake by mycelium and regenerating protoplasts of Verticillium marquandii

The ability of the filamentous fungus Verticillium marquandii for Zn²⁺ and Pb²⁺ uptake from aqueous solution was studied. The 24-h-old living mycelium bound Zn²⁺ and Pb²⁺ (206.2 and 324.5 mg/g dry weight, respectively) effectively, in contrast to a very low Zn²⁺ uptake by autoclaved mycelium (20.2 mg/g). The most effective results were noted when the metals were introduced as acetates and incubated with mycelium for 24 h in case of Zn²⁺ while Pb²⁺ achieved the maximum level of metal binding after as early as 3 h. The cell wall was the main site of effective Zn²⁺ and Pb²⁺ binding by V. marquandii mycelium (91.0–93.6% of metals were located in cell wall after 24 h of exposure). The metabolic inhibitors: antimycin A and sodium azide had a strong limitation effect on Zn²⁺ uptake by a 24-h-old living mycelium, whereas Pb²⁺ binding did not decrease to a large extent. The freshly obtained protoplasts accumulated Zn²⁺ and Pb²⁺ on a low level in comparison with cells at different stages of cell wall regeneration. The use of regenerating protoplasts showed that resynthesis of cell wall was necessary for high binding of Zn²⁺, whereas Pb²⁺ uptake on the significant level took place during cell wall regeneration. This revised version was published online in August 2006 with corrections to the Cover Date.     

Effects of Lead Ions on the Synaptic Responses of Neurons of the Rat Sympathetic Ganglion

Using intracellular recording, we studied the effects of lead ions on the synaptic responses of neurons of the superior cervical ganglion (SCG) of the rat. Three groups of SCG neurons were found; they differed from each other in directions of the changes evoked by Pb²⁺ applications and in their sensitivity to this agent. In two groups of the phasic SCG neurons, Pb²⁺ decreased the amplitude of EPSP evoked by stimulation of the cervical sympathetic nerve with EC₅₀ of (2.2 ± 0.2) · 10^-6 M and (3.55 ± 0.29) · 10^-5 M, respectively. In the tonic neurons, 2 · 10^-6 M Pb²⁺ increased the EPSP amplitude by 27 ± 2%, on average, as compared with the control values. We postulate that the specificity of responses of these three groups of SCG neurons to the action of Pb²⁺ is determined by the different subunit composition of the nicotinic cholinoreceptors in the membrane of these cells.     

Computational analysis of spiro-oxindole inhibitors of the MDM2-p53 interaction: insights and selection of novel inhibitors

Since MDM2 is an inhibitor of the p53 tumor suppressor, disrupting the MDM2-p53 interaction is a promising approach for cancer therapy. Here, we used molecular dynamics simulations followed by free energy decomposition analysis to study conformational changes in MDM2 induced by three known spiro-oxindole inhibitors. Analysis of individual energy terms suggests that van der Waals and electrostatic interactions explain much of the binding affinities of these inhibitors. Binding free energies calculated for the three inhibitors using the molecular mechanics-generalized Born surface area model were consistent with experimental data, suggesting the validity of this approach. Based on this structure-function analysis, several novel spiro-oxindole derivatives were selected and evaluated for their ability to block the MDM2-p53 interaction in vitro. These results suggest that combining in silico and experimental techniques can provide insights into the structure-function relationships of MDM2 inhibitors and guide the rational design of anticancer drugs targeting the MDM2-p53 interaction.