Beverley Hale

Molecular and cellular mechanisms of cadmium carcinogenesis.

Cadmium is a heavy metal, which is widely used in industry, affecting human health through occupational and environmental exposure. In mammals, it exerts multiple toxic effects and has been classified as a human carcinogen by the International Agency for Research on Cancer. Cadmium affects cell proliferation, differentiation, apoptosis and other cellular activities. Cd2+ does not catalyze Fenton-type reactions because it does not accept or donate electrons under physiological conditions, and it is only weakly genotoxic. Hence, indirect mechanisms are implicated in the carcinogenicity of cadmium. In this review multiple mechanisms are discussed, such as modulation of gene expression and signal transduction, interference with enzymes of the cellular antioxidant system and generation of reactive oxygen species (ROS), inhibition of DNA repair and DNA methylation, role in apoptosis and disruption of E-cadherin-mediated cell-cell adhesion. Cadmium affects both gene transcription and translation. The major mechanisms of gene induction by cadmium known so far are modulation of cellular signal transduction pathways by enhancement of protein phosphorylation and activation of transcription and translation factors. Cadmium interferes with antioxidant defense mechanisms and stimulates the production of reactive oxygen species, which may act as signaling molecules in the induction of gene expression and apoptosis. The inhibition of DNA repair processes by cadmium represents a mechanism by which cadmium enhances the genotoxicity of other agents and may contribute to the tumor initiation by this metal. The disruption of E-cadherin-mediated cell-cell adhesion by cadmium probably further stimulates the development of tumors. It becomes clear that there exist multiple mechanisms which contribute to the carcinogenicity of cadmium, although the relative weights of these contributions are difficult to estimate.

Amelioration of Ozone-Induced Oxidative Damage in Wheat Plants Grown under High Carbon Dioxide (Role of Antioxidant Enzymes).

O3-induced changes in growth, oxidative damage to protein, and specific activities of certain antioxidant enzymes were investigated in wheat plants (Triticum aestivum L. cv Roblin) grown under ambient or high CO2. High CO2 enhanced shoot biomass of wheat plants, whereas O3 exposure decreased shoot biomass. The shoot biomass was relatively unaffected in plants grown under a combination of high CO2 and O3. O3 exposure under ambient CO2 decreased photosynthetic pigments, soluble proteins, and ribulose-1,5-bisphosphate carboxylase/oxygenase protein and enhanced oxidative damage to proteins, but these effects were not observed in plants exposed to O3 under high CO2. O3 exposure initially enhanced the specific activities of superoxide dismutase, peroxidase, glutathione reductase, and ascorbate peroxidase irrespective of growth in ambient or high CO2. However, the specific activities decreased in plants with prolonged exposure to O3 under ambient CO2 but not in plants exposed to O3 under high CO2. Native gels revealed preferential changes in the isoform composition of superoxide dismutase, peroxidases, and ascorbate peroxidase of plants grown under a combination of high CO2 and O3. Furthermore, growth under high CO2 and O3 led to the synthesis of one new isoform of glutathione reductase. This could explain why plants grown under a combination of high CO2 and O3 are capable of resisting O3-induced damage to growth and proteins compared to plants exposed to O3 under ambient CO2.

Coupling the use of computer chemical speciation models and culture techniques in laboratory investigations of trace metal toxicity

Abstract The bioavailability and toxicity of a dissolved metal are closely linked to the metal’s chemical speciation in solution. A variety of inorganic and organic ligands are often used in laboratory toxicity tests to control the concentration of labile trace metal in solution. Computerised chemical speciation models based on thermodynamic principles can be used to estimate metal speciation under such experimental conditions. However, these models are sensitive to the quality of their thermodynamic databases. Detailed protocols for the incorporation of reliable equilibrium formation constants into widely available computer chemical speciation programs (e.g., MINEQL+ and MINTEQ) are provided. The examples demonstrate both the benefits and the potential pitfalls involved in the use of chemical speciation models. The application of chemical speciation modelling to metal toxicity studies is discussed and guidelines are proposed for its proper use. Both defined media and chemical speciation programs have co-existed for two decades but the combined use of these techniques has been reserved for those possessing in-depth knowledge of both chemistry and biology. The techniques presented should enable an investigator with basic biological, chemical and computing skills to design an aqueous medium and incorporate correct thermodynamic constants into a computer chemical speciation program, starting from a standardised database, thereby providing a sound framework for critically assessing the biological response of a particular test organism to a given metal.

The biotic ligand model for plants and metals: Technical challenges for field application†

To improve predictions of phytoavailable metal, the mechanistic bases of bioaccumulation and toxicity of metals to plants can be integrated into a biotic ligand model (BLM). There are a number of significant challenges to the application of the BLM to plants in soils, including reliable measurements of free ion concentrations for the metals of interest in rhizospheric soil solution, as well as other free ions, and concentrations of ligands to which the ions could bind; identification of the simplest model that can adequately predict root accumulation, and the potential for more complex models to add accuracy to the predictions; incorporating the dissociation of labile metal complexes (i.e., nonequilibrium processes) into a BLM, which is an equilibrium model; application of factors in a BLM that adequately describe translocation, in order to estimate metal concentration and speciation in plant shoots. The review concluded that the ability to estimate trace metal speciation in samples of soil solution are not likely to be better than within one order of magnitude of actual, thus this would be an additional source of uncertainty to the predictions of toxicity. Further, regulatory use of the BLM would require mechanistic bases; and, until root ligands associated with toxicity are well characterized, incorporating the ameliorative effects of competitive cations cannot be mechanistically based. As well, a functional BLM for soils with lower metal free ion activities will have to include kinetic data for metal-ligand complexes, as their association/disassociation may constitute a greater metal supply to roots than what would be predicted by the free ion concentration in soil solution. To apply the BLM to trophic transfer where metal concentration in plant shoots is the main focus, a probabilistic approach using experimentally determined root-shoot partitioning of metals might permit estimates of shoot accumulation from root data, to within one or two orders of magnitude.

Effects of cement or lime on Cd, Co, Cu, Ni, Pb, Sb and Zn mobility in field-contaminated and aged soils.

Cement or lime can be used to treat trace element contaminated soils, reducing their mobility due to increased soil pH which enhances precipitation and adsorption, and also due to pozzolanic reactions and cementation. In the present work, an alkaline and an acidic soil both containing Cd, Co, Cu, Ni, Pb, Sb and Zn from either geogenic or geogenic and anthropogenic origin were treated with cement or calcium hydroxide. Soils were then extracted with dilute HNO(3) or NaOH solution of different concentrations to obtain extracts of different pH (pH 4-12). In untreated soils, Co, Cu, Ni and Pb in solutions were detected at alkaline pH. The addition of cement or Ca(OH)(2) reduced the mobility of every trace element at high pH, but enhanced the mobility of Cd, Co, Cu, Ni, Pb and Zn at low pH. Metal mobilisation at high pH was observed for Cu in the acidic soil due to the liberation of dissolved organic matter. Below pH 6, Sb mobility was lower in the cement-treated soil compared to the untreated soil, but the same in the Ca(OH)(2) treated soil as in the control soil. Comparison with theoretical trace element precipitates suggested that the mobility of trace elements is likely reduced at high pH by encapsulation and immobilisation within the cement matrix rather then precipitation.

White birch (Betula papyrifera Marshall) foliar litter decomposition in relation to trace metal atmospheric inputs at metal-contaminated and uncontaminated sites near Sudbury, Ontario and Rouyn-Noranda, Quebec, Canada.

Decomposition of white birch (Betula papyrifera Marshall) foliar litter was examined at metal-contaminated and uncontaminated sites established along gradients of soil Cu, Ni, Pb and Zn concentrations near Sudbury, Ontario and Rouyn-Noranda, Quebec. Over an 18-month study period, a significantly lower rate of litter mass loss was observed at the Sudbury contaminated site (S1) than at the uncontaminated site (S2). This result was not duplicated at corresponding sites (RN1, RN2) in Rouyn-Noranda, despite similar levels of soil metal contaminants and atmospheric inputs. Concentrations of metals in litter increased at all sites with time. However, the greatest litter Cu and Ni concentrations were observed at S1 (188 and 192 microg/g, respectively), a result of substantial net gains of these elements from atmospheric inputs. On a per hectare basis, Cu accumulation in litter at S1 approached recommended application rates of Cu as copper sulphate for control of fungal diseases in agricultural operations, indicating that the current rate of Cu smelter emissions in Sudbury may cause the observed impairment of decomposition.

Human health risks of Pb and As exposure via consumption of home garden vegetables and incidental soil and dust ingestion: A probabilistic screening tool

The consumption of home grown vegetables may represent a significant exposure pathway for arsenic (As) and lead (Pb) relative to direct incidental ingestion of soil, thus a probabilistic screening tool for estimating these exposures was developed using regression models relating co-located soil and home garden (HG) vegetable concentrations of Pb and As established from multiple independent studies and 2-dimensional Monte Carlo analyses. For high-quantity consumers of HG vegetables (i.e., the upper 95th percentile of consumers in the general population), the HG consumption pathway can be as significant as incidental soil and dust ingestion for inorganic As and, therefore, should be considered when developing generic health-based soil criteria in residential settings. Predicted Pb Hazard Quotient (HQ) estimates among young children resulting from HG consumption were 4- to 10-fold lower than exposures resulting from direct incidental soil and dust ingestion. The difference in soil/dust ingestion rates used to characterize young children (the 95th percentile of 202 mg/d) versus a lifetime residential receptor (the 95th percentile of 30 mg/d) was a primary factor contributing to the relative differences observed between HQ and incremental lifetime cancer risk (ILCR) resulting from these two exposure pathways for lead Pb and inorganic arsenic As, respectively.

Toxicity versus accumulation for barley plants exposed to copper in the presence of metal buffers: Progress towards development of a terrestrial biotic ligand model†

Development of a terrestrial biotic ligand model (TBLM) for higher plants requires a root-Cu accumulation value that corresponds to the 50% inhibitory concentration (IC50). However, it is not yet known which of the two previously reported Cu-binding ligands on the root is associated with Cu toxicity. The aim of the present study was therefore to investigate the relationship between Cu binding to each ligand group and toxicity, so that the key toxicological site could be identified. To obtain accumulation and toxicity data that were not biased by limited Cu supply to the root, 2-d-old barley seedlings were exposed for 48 h to a range of free Cu ion activities (i.e., {Cu(2+)}) in simple exposure media buffered by nitrilotriacetic acid (NTA) or ethylenediaminetetraacetic acid (EDTA). Comparison of the amount of predicted root-bound Cu (calculated with the aqueous geochemical program PHREEQC) with root elongation data showed that toxicity likely resulted from Cu binding to low-affinity ligands, as the high-affinity ligands were approximately 99% saturated when a reduction in root elongation was first observed. For plants exposed to both NTA- and the EDTA-buffered {Cu(2+)} solutions, the root-Cu accumulation value corresponding to the IC50 was approximately 80 microg/g root dry weight, which is similar to the value obtained from previous work with wheat. The linear relationship between the amount of Cu bound to the low-affinity ligands and the percent root growth inhibition suggests that this relationship will be a robust predictor of Cu toxicity when incorporated into the TBLM, and applied to varied exposure scenarios. For the simple solutions used here, the TBLM-predicted and measured IC50 values were statistically indistinguishable.

Effects of pre-exposure to ultraviolet-B radiation on responses of tomato (Lycopersicon esculentum cv. New Yorker) to ozone in ambient and elevated carbon dioxide.

Patterns of environmental change in the biosphere include concurrent and sequential combinations of increasing ultraviolet (UV-B) and ozone (O(3)) at increasing carbon dioxide (CO(2)) levels; long-term changes are resulting mainly from stratospheric O(3) depletion, greater tropospheric O(3) photochemical synthesis, and increasing CO(2) emissions. Effects of selected combinations were evaluated in tomato (Lycopersicon esculentum cv. New Yorker) seedlings using sequential exposures to enhanced UV-B radiation and O(3) in differential CO(2) concentrations. Ambient (7.2 kJ m(-2 )day(-1)) or enhanced (13.1 kJ m(-2) day(-1)) UV-B fluences and ambient (380 microl l(-1)) or elevated (600 microl l(-1)) CO(2) were imposed for 19 days before exposure to 3-day simulated O(3) episodes with peak concentrations of 0.00, 0.08, 0.16 or 0.24 microl l(-1) O(3) in ambient or elevated CO(2). CO(2) enrichment increased dry mass, leaf area, specific leaf weight, chlorophyll concentration and UV-absorbing compounds per unit leaf area. Exposure to enhanced UV-B increased leaf chlorophyll and UV-absorbing compounds but decreased leaf area and root/shoot ratio. O(3) exposure generally inhibited growth and leaf photosynthesis and did not affect UV-absorbing compounds. The highest dose of O(3) eliminated the stimulating effect of CO(2) enrichment after ambient UV-B pre-exposure on leaf photosynthesis. Pre-exposure to enhanced UV-B mitigated O(3) damage to leaf photosynthesis at elevated CO(2).

Toxicity thresholds for oat (Avena sativa L.) grown in Ni-impacted agricultural soils near Port Colborne, Ontario, Canada

This study established Ni phytotoxicity thresholds for oat (Avena sativa L.) in four soil types, each created by blending a low and a high Ni soil, to generate a range of concentrations. The first quartile effective concentration (EC25) for soil and shoot tissue Ni concentration and reduction in shoot dry weight (DW) was determined using a Weibull function. The EC25 (for soil Ni concentration) was 1350, 1950, 1880 and > 2400 mg Ni kg-1 soil, for sand, till clay, heavy clay and organic muck, respectively. The EC25 (for shoot Ni concentration) was 71, 21, 52 and > 35 mg Ni kg-1 shoot DW, for sand, till clay, heavy clay and organic muck, respectively. Total soil Ni concentration, soil pH and soil cation exchange capacity (CEC) accounted for 70% of the variation of Ni accumulation in tissue when the data for all four of the soils were combined; this was similar to the amount of variation accounted for by fitting Ni concentration in tissue to ammonium oxalate extractable soil Ni. Manganese deficiency may have ...