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A 28-year-old female presented for evaluation of left flank pain and polyuria after having been exposed to cadmium in the jewelry manufacturing industry for approximately 3 years. This patient possessed both elevated 24-hr urinary ss2-microglobulin and elevated blood cadmium levels. Approximately 6 months after initial presentation, the patient resigned from her job due to shortness of breath, chest pain, and anxiety. Exposure to cadmium in the jewelry industry is a significant source of occupational cadmium exposure. Other occupational sources include the manufacture of nickel-cadmium batteries, metal plating, zinc and lead refining, smelting of cadmium and lead, and production of plastics. Cadmium is also an environmental pollutant that accumulates in leafy vegetables and plants, including tobacco. Major toxicities anticipated from cadmium exposure involve the renal, pulmonary, and, to a lesser extent, gastrointestinal systems. These include the development of renal proximal tubular dysfunction, glomerular damage with progressive renal disease, and respiratory symptoms including pneumonitis and emphysema. Low-level cadmium exposure has also been associated with increased urinary calcium excretion and direct bone toxicity, effects that recent research suggests may result in the development of osteoporosis. The body burden of cadmium, over half of which may reside in the kidneys, is most often measured through the use of urinary cadmium levels. Blood cadmium measurements generally reflect current or recent exposure and are especially useful in cases with a short exposure period and only minimal accumulation of cadmium in the kidneys. Both ss2-microglobulin and alpha1-microglobulin serve as organ-specific, early-effect biomarkers of tubular proteinuria and thus play a role in identifying early signs of cadmium-induced renal damage in those with potential exposures. In addition to ensuring workplace compliance with Occupational Safety and Health Administration-mandated monitoring and screening measures, it is prudent for those with cadmium exposure to maintain adequate intake of both iron and calcium, appropriate measures even in the absence of exposure.

Cadmium is an important heavy metal pollutant. For this study, we investigated the effects of cadmium exposure on the oxidative stress responses of Xanthomonas campestris, a soil and plant pathogenic bacterium. The exposure of X. campestris to low concentrations of cadmium induces cross-protection against subsequent killing treatments with either H2O2 or the organic hydroperoxide tert-butyl hydroperoxide (tBOOH), but not against the superoxide generator menadione. The cadmium-induced resistance to peroxides is due to the metal's ability to induce increased levels of peroxide stress protective enzymes such as alkyl hydroperoxide reductase (AhpC), monofunctional catalase (KatA), and organic hydroperoxide resistance protein (Ohr). Cadmium-induced resistance to H2O2 is dependent on functional OxyR, a peroxide-sensing transcription regulator. Cadmium-induced resistance to tBOOH shows a more complex regulatory pattern. The inactivation of the two major sensor-regulators of organic hydroperoxide, OxyR and OhrR, only partially inhibited cadmium-induced protection against tBOOH, suggesting that these genes do have some role in the process. However, other, as yet unknown mechanisms are involved in inducible organic hydroperoxide protection. Furthermore, we show that the cadmium-induced peroxide stress response is mediated by the metal's ability to predominately cause an increase in intracellular concentrations of organic hydroperoxide and, in part, H2O2. Analyses of various mutants of peroxide-metabolizing enzymes suggested that this increase in organic hydroperoxide levels is, at least in part, responsible for cadmium toxicity in Xanthomonas.

Cadmium is a worldwide environmental toxicant responsible for a range of human diseases including cancer. Cellular injury from cadmium is minimized by stress-responsive detoxification mechanisms. We explored the genetic requirements for cadmium tolerance by individually screening mutants from the fission yeast (Schizosaccharomyces pombe) haploid deletion collection for inhibited growth on agar growth media containing cadmium. Cadmium-sensitive mutants were further tested for sensitivity to oxidative stress (hydrogen peroxide) and osmotic stress (potassium chloride). Of 2649 mutants screened, 237 were sensitive to cadmium, of which 168 were cadmium specific. Most were previously unknown to be involved in cadmium tolerance. The 237 genes represent a number of pathways including sulfate assimilation, phytochelatin synthesis and transport, ubiquinone (Coenzyme Q10) biosynthesis, stress signaling, cell wall biosynthesis and cell morphology, gene expression and chromatin remodeling, vacuole function, and intracellular transport of macromolecules. The ubiquinone biosynthesis mutants are acutely sensitive to cadmium but only mildly sensitive to hydrogen peroxide, indicating that Coenzyme Q10 plays a larger role in cadmium tolerance than just as an antioxidant. These and several other mutants turn yellow when exposed to cadmium, suggesting cadmium sulfide accumulation. This phenotype can potentially be used as a biomarker for cadmium. There is remarkably little overlap with a comparable screen of the Saccharomyces cerevisiae haploid deletion collection, indicating that the two distantly related yeasts utilize significantly different strategies for coping with cadmium stress. These strategies and their relation to cadmium detoxification in humans are discussed.

Oxidative stress has been implicated to play a role, at least in part, in pathogenesis of many disease conditions and toxicities in animals. Overproduction of reactive oxygen species and free radicals beyond the cells intrinsic capacity to neutralize following xenobiotics exposure leads to a state of oxidative stress and resultant damages of lipids, protein, and DNA. Lead and cadmium are the common environmental heavy metal pollutants and have widespread distribution. Both natural and anthropogenic sources including mining, smelting, and other industrial processes are responsible for human and animal exposure. These pollutants, many a times, are copollutants leading to concurrent exposure to living beings and resultant synergistic deleterious health effects. Several mechanisms have been explained for the damaging effects on the body system. Of late, oxidative stress has been implicated in the pathogenesis of the lead- and cadmium-induced pathotoxicity. Several ameliorative measures to counteract the oxidative damage to the body system aftermath or during exposure to these toxicants have been assessed with the use of antioxidants. The present review focuses on mechanism of lead- and cadmium-induced oxidate damages and the ameliorative measures to counteract the oxidative damage and pathotoxicity with the use of supplemented antioxidants for their beneficial effects.

Cadmium, a widespread toxic pollutant of occupational and environmental concern, is a known human carcinogen. The prostate is a potential target for cadmium carcinogenesis, although the underlying mechanisms are still unclear. Furthermore, cadmium may induce cell death by apoptosis in various cell types, and it has been hypothesized that a key factor in cadmium-induced malignant transformation is acquisition of apoptotic resistance. We investigated the in vitro effects produced by cadmium exposure in normal or tumor cells derived from human prostate epithelium, including RWPE-1 and its cadmium-transformed derivative CTPE, the primary adenocarcinoma 22Rv1 and CWR-R1 cells and LNCaP, PC-3 and DU145 metastatic cancer cell lines. Cells were treated for 24 hours with different concentrations of CdCl2 and apoptosis, cell cycle distribution and expression of tumor suppressor proteins were analyzed. Subsequently, cellular response to cadmium was evaluated after siRNA-mediated p53 silencing in wild type p53-expressing RWPE-1 and LNCaP cells, and after adenoviral p53 overexpression in p53-deficient DU145 and PC-3 cell lines. The cell lines exhibited different sensitivity to cadmium, and 24-hour exposure to different CdCl2 concentrations induced dose- and cell type-dependent apoptotic response and inhibition of cell proliferation that correlated with accumulation of functional p53 and overexpression of p21 in wild type p53-expressing cell lines. On the other hand, p53 silencing was able to suppress cadmium-induced apoptosis. Our results demonstrate that cadmium can induce p53-dependent apoptosis in human prostate epithelial cells and suggest p53 mutation as a possible contributing factor for the acquisition of apoptotic resistance in cadmium prostatic carcinogenesis.

Background

Cadmium is a widespread environmental pollutant that has been shown to exert toxic effects on kidney and bones in humans after long-term exposure. Urinary cadmium concentration is considered a good biomarker of accumulated cadmium in kidney, and diet is the main source of cadmium among nonsmokers.

Objective

Modeling the link between urinary cadmium and dietary cadmium intake is a key step in the risk assessment of long-term cadmium exposure. There is, however, little knowledge on how this link may vary, especially for susceptible population strata.

Methods

We used a large population-based study (the Swedish Mammography Cohort), with repeated dietary intake data covering a period of 20 years, to compare estimated dietary cadmium intake with urinary cadmium concentrations on an individual basis. A modified version of the Nordberg-Kjellström model and a one-compartment model were evaluated in terms of their predictions of urinary cadmium. We integrated the models and quantified the between-person variability of cadmium half-life in the population. Finally, sensitivity analyses and Monte Carlo simulations were performed to illustrate how the latter model could serve as a robust tool supporting the risk assessment of cadmium in humans.

Results

The one-compartment population model appeared to be an adequate modeling option to link cadmium intake to urinary cadmium and to describe the population variability. We estimated the cadmium half-life to be about 11.6 years, with about 25% population variability.

Conclusions

Population toxicokinetic models can be robust and useful tools for risk assessment of chemicals, because they allow quantification and integration of population variability in toxicokinetics.

Many heavy metals, including nickel (Ni), cadmium (Cd), and chromium (Cr) are toxic industrial chemicals with an exposure risk in both occupational and environmental settings that may cause harmful outcomes. While these substances are known to produce adverse health effects leading to disease or health problems, the detailed mechanisms remain unclear. To elucidate the processes involved in the toxicity of nickel, cadmium, and chromium at the molecular level and to perform a comparative analysis, H4-II-E-C3 rat liver-derived cell lines were treated with soluble salts of each metal using concentrations derived from viability assays, and gene expression patterns were determined with DNA microarrays. We identified both common and unique biological responses to exposure to the three metals. Nickel, cadmium, chromium all induced oxidative stress with both similar and unique genes and pathways responding to this stress. Although all three metals are known to be genotoxic, evidence for DNA damage in our study only exists in response to chromium. Nickel induced a hypoxic response as well as inducing genes involved in chromatin structure, perhaps by replacing iron in key proteins. Cadmium distinctly perturbed genes related to endoplasmic reticulum stress and invoked the unfolded protein response leading to apoptosis. With these studies, we have completed the first gene expression comparative analysis of nickel, cadmium, and chromium in H4-II-E-C3 cells.

Although oxidative stress has been proposed as a mechanism of lead and cadmium toxicity mostly based on in vitro experiments or animal studies, it is uncertain whether this mechanism is relevant in the pathogenesis of lead- or cadmium-related diseases in the general population with low environmental exposure to lead and cadmium. We examined associations of blood lead and urinary cadmium levels with oxidative stress markers of serum γ-glutamyltransferase (GGT), vitamin C, carotenoids, and vitamin E among 10,098 adult participants in the third U.S. National Health and Nutrition Examination Survey. After adjusting for race, sex, and age (plus serum total cholesterol in the case of serum carotenoids and vitamin E), blood lead and urinary cadmium levels both showed graded associations, positive with serum GGT and inverse with serum vitamin C, carotenoids, and vitamin E (p for trend < 0.01, respectively). These associations were consistently observed among most subgroups: non-Hispanic white, non-Hispanic black, men, women, all age groups, non-drinkers, drinkers, nonsmokers, ex-smokers, current smokers, and body mass index (< 25, 25–29.9, and ≥30). The strong association of blood lead and urinary cadmium levels with oxidative stress markers in this population suggests that oxidative stress should be considered in the pathogenesis of lead- and cadmium-related diseases even among people with low environmental exposure to lead and cadmium.

Cadmium is a toxic heavy metal which is environmentally and occupationally relevant. The mechanisms underlying cadmium-induced autophagy are not yet completely understood. The present study shows that cadmium induces autophagy, as demonstrated by the increase of LC3-II formation and the GFP-LC3 puncta cells. The induction of autophagosomes was directly visualized by electron microscopy in cadmium-exposed skin epidermal cells. Blockage of LKB1 or AMPK by siRNA transfection suppressed cadmium-induced autophagy. Cadmium-induced autophagy was inhibited in dominant-negative AMPK-transfected cells, whereas it was accelerated in cells transfected with the constitutively active form of AMPK. mTOR signaling, a negative regulator of autophagy, was downregulated in cadmium-exposed cells. In addition, cadmium generated reactive oxygen species (ROS) at relatively low levels, and caused poly(ADP-ribose) polymerase-1 (PARP) activation and ATP depletion. Inhibition of PARP by pharmacological inhibitors or its siRNA transfection suppressed ATP reduction and autophagy in cadmium-exposed cells. Furthermore, cadmium-induced autophagy signaling was attenuated by either exogenous addition of catalase and superoxide dismutase, or by overexpression of these enzymes. Consequently, these results suggest that cadmium-mediated ROS generation causes PARP activation and energy depletion, and eventually induces autophagy through the activation of LKB1-AMPK signaling and the down-regulation of mTOR in skin epidermal cells.

Exposure to cadmium results in disturbances in cell homeostasis in all living organisms. The first response to stress factors, including cadmium, is activation of signal transduction pathways that mobilize cell defense mechanisms. The aim of this review is a comparison between the signaling network triggered by Cd in plants and animals. Despite differences in the structure and physiology of plant and animal cells, their cadmium signal transduction pathways share many common elements. These elements include signaling molecules such as ROS, Ca2+ and NO, the involvement of phospholipase C, mitogen-activated protein kinase cascades, and activation of transcription factors. Undoubtedly, both animals and plants also possess specific signaling pathways. In case of animals, Wnt/β-catenin, sonic hedgehog and oestorgen signaling are engaged in the transduction of cadmium signal. Plant specific signal transduction pathways include signaling mediated by plant hormones. The role of ethylene and jasmonic, salicylic and abscisic acid in plant response to cadmium is also discussed.

Understanding the mechanism of cadmium (Cd) accumulation in plants is important to help reduce its potential toxicity to both plants and humans through dietary and environmental exposure. Here, we report on a study to uncover the genetic basis underlying natural variation in Cd accumulation in a world-wide collection of 349 wild collected Arabidopsis thaliana accessions. We identified a 4-fold variation (0.5–2 µg Cd g−1 dry weight) in leaf Cd accumulation when these accessions were grown in a controlled common garden. By combining genome-wide association mapping, linkage mapping in an experimental F2 population, and transgenic complementation, we reveal that HMA3 is the sole major locus responsible for the variation in leaf Cd accumulation we observe in this diverse population of A. thaliana accessions. Analysis of the predicted amino acid sequence of HMA3 from 149 A. thaliana accessions reveals the existence of 10 major natural protein haplotypes. Association of these haplotypes with leaf Cd accumulation and genetics complementation experiments indicate that 5 of these haplotypes are active and 5 are inactive, and that elevated leaf Cd accumulation is associated with the reduced function of HMA3 caused by a nonsense mutation and polymorphisms that change two specific amino acids.

Author Summary

Cadmium (Cd) is a potentially toxic metal pollutant that threatens food quality and human health in many regions of the world. Plants have evolved mechanisms for the acquisition of essential metals such as zinc and iron from the soil. Though often quite specific, such mechanisms can also lead to the accumulation of Cd by plants. Understanding natural variation in the processes that contribute to Cd accumulation in food crops could help minimize the human health risk posed. We have discovered that DNA sequence changes at a single gene, which encodes the Heavy Metal ATPase 3 (HMA3), drives the variation in Cd accumulation we observe in a world-wide sample of Arabidopsis thaliana. We identified 10 major HMA3 protein variants, of which five contribute to reduce Cd accumulation in leaves of A. thaliana.

Cadmium is a non-essential toxic metal in mammals. Its toxicity is mainly caused by interactions with cellular proteins that result in protein dysfunction and the disturb normal cellular functions. Glutathione (GSH) has been reported to play a role in cadmium resistance by serving as a cofactor for MRP1/GS-X pump-mediated cadmium elimination. To further investigate the role of GSH in cadmium toxicity, we carried out comparative study using small cell lung cancer derived cell lines, SR3A, and those that were stably transfected with glutamate cysteine ligase catalytic subunit (GCLC), a rate limiting enzyme in GSH biosynthesis. These GCLC-stably transfected cell lines produced higher levels of GSH and were more resistant to cadmium toxicity than the parental cell line was. The rates of cadmium uptake were reduced in these GCLC-transfected cell lines, which were associated with down regulation of the cadmium transporter ZIP8/SLC39A8. Further analyses demonstrated that Sp1 binding site at the proximal promoter region of ZIP8 was sensitive to the GSH level, and that the expression level of transcription factor Sp1 was reduced by increased GSH levels. We also demonstrated that low concentrations of cadmium exposure downregulated ZIP8 expression with concomitant reduction of Sp1 expression. Taken together, these results demonstrate the importance of Sp1 in the regulation of ZIP8 expression. More important, our results reveal a new mechanism by which elevated GSH levels confer cadmium resistance by downregulation of ZIP8 expression through the suppression of Sp1.

Background: Cadmium, a common food pollutant, alters DNA methylation in vitro. Epigenetic effects might therefore partly explain cadmium’s toxicity, including its carcinogenicity; however, human data on epigenetic effects are lacking.

Objective: We evaluated the effects of dietary cadmium exposure on DNA methylation, considering other environmental exposures, genetic predisposition, and gene expression.

Methods: Concentrations of cadmium, arsenic, selenium, and zinc in blood and urine of nonsmoking women (n = 202) from the northern Argentinean Andes were measured by inductively coupled mass spectrometry. Methylation in CpG islands of LINE-1 (long interspersed nuclear element-1; a proxy for global DNA methylation) and promoter regions of p16 [cyclin-dependent kinase inhibitor 2A (CDKN2A)] and MLH1 (mutL homolog 1) in peripheral blood were measured by bisulfite polymerase chain reaction pyrosequencing. Genotyping (n = 172) for the DNA (cytosine-5-)-methyltransferase 1 gene (DNMT1 rs10854076 and rs2228611) and DNA (cytosine-5-)-methyltransferase 3 beta gene (DNMT3B rs2424913 and rs2424932) was performed with Sequenom iPLEX GOLD SNP genotyping; and gene expression (n = 90), with DirectHyb HumanHT-12 (version 3.0).

Results: Cadmium exposure was low: median concentrations in blood and urine were 0.36 and 0.23 µg/L, respectively. Urinary cadmium (natural log transformed) was inversely associated with LINE-1 methylation (β = –0.50, p = 0.0070; β = –0.44, p = 0.026, adjusted for age and coca chewing) but not with p16 or MLH1 methylation. Both DNMT1 rs10854076 and DNMT1 rs2228611 polymorphisms modified associations between urinary cadmium and LINE-1 (p-values for interaction in adjusted models were 0.045 and 0.064, respectively). The rare genotypes demonstrated stronger hypomethylation with increasing urinary cadmium concentrations. Cadmium was inversely associated with DNMT3B (rS = –0.28, p = 0.0086) but not with DNMT1 expression (rS = –0.075, p = 0.48).

Conclusion: Environmental cadmium exposure was associated with DNA hypomethylation in peripheral blood, and DNMT1 genotypes modified this association. The role of epigenetic modifications in cadmium-associated diseases needs clarification.

The use of plants for rehabilitation of heavy-metal-contaminated environments is an emerging area of interest because it provides an ecologically sound and safe method for restoration and remediation. Although a number of plant species are capable of hyperaccumulation of heavy metals, the technology is not applicable for remediating sites with multiple contaminants. A clever solution is to combine the advantages of microbe-plant symbiosis within the plant rhizosphere into an effective cleanup technology. We demonstrated that expression of a metal-binding peptide (EC20) in a rhizobacterium, Pseudomonas putida 06909, not only improved cadmium binding but also alleviated the cellular toxicity of cadmium. More importantly, inoculation of sunflower roots with the engineered rhizobacterium resulted in a marked decrease in cadmium phytotoxicity and a 40% increase in cadmium accumulation in the plant root. Owing to the significantly improved growth characteristics of both the rhizobacterium and plant, the use of EC20-expressing P. putida endowed with organic-degrading capabilities may be a promising strategy to remediate mixed organic-metal-contaminated sites.

Background

Cadmium is a widespread environmental pollutant with adverse effects on kidneys and bone, but with insufficiently elucidated public health consequences such as risk of end-stage renal diseases, fractures and cancer. Urinary cadmium is considered a valid biomarker of lifetime kidney accumulation from overall cadmium exposure and thus used in the assessment of cadmium-induced health effects. We aimed to assess the relationship between dietary cadmium intake assessed by analyses of duplicate food portions and cadmium concentrations in urine and blood, taking the toxicokinetics of cadmium into consideration.

Methods

In a sample of 57 non-smoking Swedish women aged 20-50 years, we assessed Pearson's correlation coefficients between: 1) Dietary intake of cadmium assessed by analyses of cadmium in duplicate food portions collected during four consecutive days and cadmium concentrations in urine, 2) Partial correlations between the duplicate food portions and urinary and blood cadmium concentrations, respectively, and 3) Model-predicted urinary cadmium concentration predicted from the dietary intake using a one-compartment toxicokinetic model (with individual data on age, weight and gastrointestinal cadmium absorption) and urinary cadmium concentration.

Results

The mean concentration of cadmium in urine was 0.18 (+/- s.d.0.12) μg/g creatinine and the model-predicted urinary cadmium concentration was 0.19 (+/- s.d.0.15) μg/g creatinine. The partial Pearson correlations between analyzed dietary cadmium intake and urinary cadmium or blood concentrations were r = 0.43 and 0.42, respectively. The correlation between diet and urinary cadmium increased to r = 0.54 when using a one-compartment model with individual gastrointestinal cadmium absorption coefficients based on the women's iron status.

Conclusions

Our results indicate that measured dietary cadmium intake can reasonably well predict biomarkers of both long-term kidney accumulation (urine) and short-term exposure (blood). The predictions are improved when taking data on the iron status into account.

Summary

Iron, zinc, copper and manganese are essential metals for cellular enzyme functions while cadmium, mercury and the metalloid arsenic lack any biological function. Both, essential and non-essential metals and metalloids are extremely reactive and toxic. Therefore, plants have acquired specialized mechanisms to sense, transport and maintain essential metals within physiological concentrations and to detoxify non-essential metals and metalloids. This review focuses on the recent identification of transporters that sequester cadmium and arsenic in vacuoles and the mechanisms mediating the partitioning of these metal(loid)s between roots and shoots. We further discuss recent models of phloem-mediated long-distance transport, seed accumulation of Cd and As and recent data demonstrating that plants posses a defined transcriptional response that allow plants to preserve metal homeostasis. This research is instrumental for future engineering of reduced toxic metal(loid) accumulation in edible crop tissues as well as for improved phytoremediation technologies.

Cadmium is a toxic heavy metal ubiquitously present in the environment and subsequently in the human diet. Cadmium has been proposed to disrupt the endocrine system, targeting in particular the estrogen signaling pathway already at environmentally relevant concentrations. Thus far, the reports on the binding affinity of cadmium towards human estrogen receptor alpha (hERα) have been contradicting, as have been the reports on the in vivo estrogenicity of cadmium. Hence, the mode of interaction between cadmium and the receptor remains unclear. Here, we investigated the interaction between cadmium and hERα on a molecular level by applying a novel, label-free biosensor technique based on reflectometric interference spectroscopy (RIfS). We studied the binding of cadmium to hERα, and the conformation of the receptor following cadmium treatment. Our data reveals that cadmium interacts with the ligand binding domain (LBD) of the ERα and affects the conformation of the receptor. However, the binding event, as well as the induced conformation change, greatly depends on the accessibility of the cysteine tails in the LBD. As the LBD cysteine residues have been reported as targets of post-translational modifications in vivo, we present a hypothesis according to which different cellular pools of ERα respond to cadmium differently. Our proposed theory could help to explain some of the previously contradicting results regarding estrogen-like activity of cadmium.

Plants are useful in studies of metal toxicity, because their physiological responses to different metals are correlated with the metal exposure dose and chemical state. Moreover a network of proteins and biochemical cascades that may lead to a controlled homeostasis of metals has been identified in many plant species. This paper focuses on the global protein variations that occur in a Populus nigra spp. clone (Poli) that has an exceptional tolerance to the presence of cadmium. Protein separation was based on a two-dimensional liquid chromatography technique. A subset of 20 out of 126 peaks were identified as being regulated differently under cadmium stress and were fingerprinted by MALDI-TOF. Proteins that were more abundant in the treated samples were located in the chloroplast and in the mitochondrion, suggesting the importance of these organelles in the response and adaptation to metal stress.

Background

Arbuscular mycorrhizal (AM) fungi, which engage a mutualistic symbiosis with the roots of most plant species, have received much attention for their ability to alleviate heavy metal stress in plants, including cadmium (Cd). While the molecular bases of Cd tolerance displayed by mycorrhizal plants have been extensively analysed in roots, very little is known regarding the mechanisms by which legume aboveground organs can escape metal toxicity upon AM symbiosis. As a model system to address this question, we used Glomus irregulare-colonised Medicago truncatula plants, which were previously shown to accumulate and tolerate heavy metal in their shoots when grown in a substrate spiked with 2 mg Cd kg-1.

Results

The measurement of three indicators for metal phytoextraction showed that shoots of mycorrhizal M. truncatula plants have a capacity for extracting Cd that is not related to an increase in root-to-shoot translocation rate, but to a high level of allocation plasticity. When analysing the photosynthetic performance in metal-treated mycorrhizal plants relative to those only Cd-supplied, it turned out that the presence of G. irregulare partially alleviated the negative effects of Cd on photosynthesis. To test the mechanisms by which shoots of Cd-treated mycorrhizal plants avoid metal toxicity, we performed a 2-DE/MALDI/TOF-based comparative proteomic analysis of the M. truncatula shoot responses upon mycorrhization and Cd exposure. Whereas the metal-responsive shoot proteins currently identified in non-mycorrhizal M. truncatula indicated that Cd impaired CO2 assimilation, the mycorrhiza-responsive shoot proteome was characterised by an increase in photosynthesis-related proteins coupled to a reduction in glugoneogenesis/glycolysis and antioxidant processes. By contrast, Cd was found to trigger the opposite response coupled the up-accumulation of molecular chaperones in shoot of mycorrhizal plants relative to those metal-free.

Conclusion

Besides drawing a first picture of shoot proteome modifications upon AM symbiosis and/or heavy metal stress in legume plants, the current work argues for allocation plasticity as the main driving force for Cd extraction in aboveground tissues of M. truncatula upon mycorrhization. Additionally, according to the retrieved proteomic data, we propose that shoots of mycorrhizal legume plants escape Cd toxicity through a metabolic shift implying the glycolysis-mediated mobilization of defence mechanisms at the expense of the photosynthesis-dependent symbiotic sucrose sink.

Plants cope with cadmium (Cd) stress by complexation with phytochelatins (Pc), metallothioneins and glutathione and sequestration within vacuoles. Especially glutathione was found to play a major role in Cd detoxification as Cd shows a high binding affinity towards thiols and as glutathione is a precursor for Pc synthesis. In the present study, we have used an immunohistochemical approach combined with computer-supported transmission electron microscopy in order to measure changes in the subcellular distribution of glutathione during Cd-stress in mesophyll cells and cells of different glandular trichomes (long and short stalked) of Cucurbita pepo L. subsp. pepo var. styriacaGreb. Even though no ultrastructural alterations were observed in leaf and glandular trichome cells after the treatment of plants with 50 µM cadmium chloride (CdCl2) for 48 h, all cells showed a large decrease in glutathione contents. The strongest decrease was found in nuclei and the cytosol (up to 76%) in glandular trichomes which are considered as a major side of Cd accumulation in leaves. The ratio of glutathione between the cytosol and nuclei and the other cell compartments was strongly decreased only in glandular trichomes (more than 50%) indicating that glutathione in these two cell compartments is especially important for the detoxification of Cd in glandular trichomes. Additionally, these data indicate that large amounts of Cd are withdrawn from nuclei during Cd exposure. The present study gives a detailed insight into the compartment-specific importance of glutathione during Cd exposure in mesophyll cells and glandular trichomes of C. pepo L. plants.

The water hyacinth (Eichhornia crassipes) may be used as a sensitive biological indicator for continuously monitoring trace quantities of toxic heavy metals in aquatic systems. A river water system polluted with cadmium was simulated while other factors of temperature, day-night cycle, water quality, and light intensity remained constant. When the water hyacinth is maintained in river water containing 0.001 mg/l. of cadmium chloride, the plant's root system will concentrate this element at an average rate of 0.9, 1.4, and 3.0 μg Cd/g root dry weight after 24, 48, and 72 hr exposure periods, respectively. At a higher cadmium concentration of 0.01 mg/l., cadmium was concentrated in the roots much faster to levels of 6.8, 13.6, and 39.1 μg/g root after 4, 8, and 24 hr exposure periods, respectively. At initial concentrations of 0.05 mg/l. cadmium, the roots contained 29.5, 48.8, and 156 μg/g root following 4, 8, and 24 hr exposure periods, respectively. During these same time intervals, the water hyacinth sorbed 56.7, 153, and 281 μg/g root when the initial cadmium concentration was increased to 0.10 mg/l.

The water hyacinth tops can also assist in the monitoring process when cadmium contamination levels are 0.10 mg/l. and greater. At this initial cadmium concentration, cadmium is translocated into the tops. After 8 hr, the tops averaged 1.1 μg/g top. After 24 hr, this concentration was increased to 6.1 μg/g top.

Cells have developed a variety of mechanisms to respond to heavy metal exposure. Here, we show that the yeast ubiquitin ligase SCFMet30 plays a central role in the response to two of the most toxic environmental heavy metal contaminants, namely, cadmium and arsenic. SCFMet30 inactivates the transcription factor Met4 by proteolysis-independent polyubiquitination. Exposure of yeast cells to heavy metals led to activation of Met4 as indicated by a complete loss of ubiquitinated Met4 species. The association of Met30 with Skp1 but not with its substrate Met4 was inhibited in cells treated with cadmium. Cadmium-activated Met4 induced glutathione biosynthesis as well as genes involved in sulfuramino acid synthesis. Met4 activation was important for the cellular response to cadmium because mutations in various components of the Met4-transcription complex were hypersensitive to cadmium. In addition, cell cycle analyses revealed that cadmium induced a delay in the transition from G1 to S phase of the cell cycle and slow progression through S phase. Both cadmium and arsenic induced phosphorylation of the cell cycle checkpoint protein Rad53. Genetic analyses demonstrated a complex effect of cadmium on cell cycle regulation that might be important to safeguard cellular and genetic integrity when cells are exposed to heavy metals.

Genomic phenotyping was used to assess the role of all non-essential S. cerevisiae proteins in modulating cell viability after exposure to cadmium, nickel and other metals.

Background

The cellular mechanisms that underlie metal toxicity and detoxification are rather variegated and incompletely understood. Genomic phenotyping was used to assess the roles played by all nonessential Saccharomyces cerevisiae proteins in modulating cell viability after exposure to cadmium, nickel, and other metals.

Results

A number of novel genes and pathways that affect multimetal as well as metal-specific tolerance were discovered. Although the vacuole emerged as a major hot spot for metal detoxification, we also identified a number of pathways that play a more general, less direct role in promoting cell survival under stress conditions (for example, mRNA decay, nucleocytoplasmic transport, and iron acquisition) as well as proteins that are more proximally related to metal damage prevention or repair. Most prominent among the latter are various nutrient transporters previously not associated with metal toxicity. A strikingly differential effect was observed for a large set of deletions, the majority of which centered on the ESCRT (endosomal sorting complexes required for transport) and retromer complexes, which - by affecting transporter downregulation and intracellular protein traffic - cause cadmium sensitivity but nickel resistance.

Conclusion

The data show that a previously underestimated variety of pathways are involved in cadmium and nickel tolerance in eukaryotic cells. As revealed by comparison with five additional metals, there is a good correlation between the chemical properties and the cellular toxicity signatures of various metals. However, many conserved pathways centered on membrane transporters and protein traffic affect cell viability with a surprisingly high degree of metal specificity.

Purpose

Mammographic density (MD), a strong marker of breast cancer risk, is influenced by genetic, environmental, and hormonal factors. Cadmium, a persistent and widespread environmental pollutant, has been associated with risk of breast cancer, and laboratory evidence suggests cadmium is a carcinogen in the breast. We investigated the hypothesis that cadmium exposure is associated with higher MD.

Methods

In a cross-sectional study of MD and urinary cadmium concentration, percentage MD (MD%) and Breast Imaging-Reporting and Data Systems (BI-RADS ®) density category were determined from screening mammograms of 190 premenopausal women ages 40–45 years. Women completed a health questionnaire, and the cadmium content of spot urine samples was measured with inductively-coupled plasma mass spectrometry and corrected for urine creatinine. Urinary cadmium concentrations are thought to reflect exposure to cadmium over a period of 20–30 years. Multivariable linear regression and logistic regression were used to estimate the strength of association between urinary cadmium and mammographic breast density.

Results

Adjusted mean MD% among women in the upper tertile of creatinine-corrected urine cadmium was 4.6% higher (95% confidence interval (CI): −2.3 to 11.6%) than in women in the lowest cadmium tertile. Each two-fold increase in urine cadmium was associated with higher odds of MD% in the upper tertile (odds ratio(OR): 1.29, 95% CI: 0.82–2.02) or a BI-RADS category rating of “extremely dense” (OR: 1.75, 95% CI: 1.14–2.70). Stronger associations were observed among nulliparous women, and current or former smokers.

Conclusions

Exposure to cadmium may be associated with increased breast density in premenopausal women.

Contaminants such as cadmium, bisphenol A and lead pollute our environment and affect male reproductive function. There is evidence that toxicant exposure adversely affects fertility. Cadmium and bisphenol A exert their effects in the testis by perturbing blood-testis barrier function, which in turn affects germ cell adhesion in the seminiferous epithelium because of a disruption of the functional axis between these sites. In essence, cadmium mediates its adverse effects at the blood-testis barrier by disrupting cell adhesion protein complexes, illustrating that toxicants can dismantle cell junctions in the testis. Herein, we will discuss how environmental toxicants may affect reproductive function. We will also examine how these adverse effects on fertility may be mediated in part by adipose tissue and bone. Lastly, we will briefly discuss how toxicant-induced damage may be effectively managed so that fertility can be maintained. It is hoped that this information will offer a new paradigm for future studies.