Cadmium carcinogenesis

Cadmium is a heavy metal of considerable environmental and occupational concern. Cadmium compounds are classified as human carcinogens by several regulatory agencies. The most convincing data that cadmium is carcinogenic in humans comes from studies indicating occupational cadmium exposure is associated with lung cancer. Cadmium exposure has also been linked to human prostate and renal cancer, although this linkage is weaker than for lung cancer. Other target sites of cadmium carcinogenesis in humans, such as liver, pancreas and stomach, are considered equivocal. In animals, cadmium effectively induces cancers at multiple sites and by various routes. Cadmium inhalation in rats induces pulmonary adenocarcinomas, in accord with its role in human lung cancer. Cadmium can induce tumors and/or preneoplastic lesions within the rat prostate after ingestion or injection. At relatively high doses, cadmium induces benign testicular tumors in rats, but these appear to be due to early toxic lesions and loss of testicular function, rather than from a specific carcinogenic effect of cadmium. Like many other metals, cadmium salts will induce mesenchymal tumors at the site of subcutaneous (s.c.) or intramuscular (i.m.) injections, but the human relevance of these is dubious. Other targets of cadmium in rodents include the liver, adrenal, pancreas, pituitary, and hematopoietic system. With the exception of testicular tumors in rodents, the mechanisms of cadmium carcinogenesis are poorly defined. Cadmium can cause any number of molecular lesions that would be relevant to oncogenesis in various cellular model systems. Most studies indicate cadmium is poorly mutagenic and probably acts through indirect or epigenetic mechanisms, potentially including aberrant activation of oncogenes and suppression of apoptosis.     

Cadmium bioavailability

Cadmium slowly accumulates in the liver and kidney and has a long biological half-life, estimated to be 2-3 decades in the kidney. If the kidney cadmium concentration reaches a critically high level, proximal tubular damage results, which can be followed by severe bone mineral loss. There are only a few measurements of cadmium bioavailability in foods; however, the data are indicative of lower utilization from foods than from inorganic salts. In animal tissues cadmium is bound primarily to a heat-resistant small protein with a high cysteine content (metallothionein), whereas little is known about the form in which cadmium occurs in the edible parts of plants. Low intakes of many nutrients exacerbate the effects of cadmium and supplemental intakes are protective. Newborn and young animals absorb much higher quantities of cadmium than adults. There is some evidence in animals that females may be more adversely affected than males. Itai-itai disease, a painful disease with kidney damage and bone demineralization, occurred in elderly Japanese women who had borne several children and who were exposed to cadmium via food and drinking water. Inasmuch as cadmium in the U.S. food supply affords an estimated safety factor of only 4- to 15-fold, it is important to establish factors that affect the bioavailability of cadmium from foods.     

Compartmentation of Cadmium and Iron in Mesembryanthemum crystallinum Plants during the Adaptation to Cadmium Stress

The common ice plants (Mesembryanthemum crystallinum) at the stage of five leaf pairs were exposed to cadmium chloride solutions (1, 0.1, and 0.01 mM) under the conditions of water culture. After five days, the partition of cadmium and iron in the plant organs and in the cell structures of the apical root region were investigated. Plant adaptation to excess cadmium in the environment was assessed by an increase in the leaf and root weight, a change in peroxidase activity, and an accumulation of proline. The common ice plant accumulated cadmium mainly in the root system. At a high concentration of cadmium in the nutrient solution (1 mM), its content in the root exceeded 2 g/kg fr wt, while at a concentration of 0.01 mM, it was as low as 10 mg/kg. Dithizone staining of transverse sections of the root apical region showed that, after a 48-h-long exposure of plants to 0.1 mM cadmium chloride, cadmium was localized in the cell walls of endodermis and metaxylem. The level of cadmium in leaves varied from 0.5 to 18 mg/kg fr wt. However, there was only a weak correlation between cadmium accumulation and the extent of a biomass decrease in the leaves of various stories, when cadmium concentration in the medium (1 mM cadmium chloride) was toxic. This fact could be related to a marked efflux of endogenous iron from old leaves into the young ones and to a change in the cadmium/iron ratio in the tissues. Proline accumulation in the third leaf pair and in the roots occurred at a relatively low cadmium content (10–12 mg/kg fr wt) in these organs. Maxima of activity of all three forms of peroxidase, viz., soluble, ionically-bound, and covalently-bound peroxidases, in roots were found at a high accumulation of cadmium in these organs (45 mg/kg fr wt). These maxima exceeded 3–4-fold the activity in aging leaves containing 5 mg cadmium/kg fr wt. A decrease in peroxidase activity in leaves was accompanied by a 3.3-fold decrease in iron content; thus, it could be caused by a deficiency of available iron necessary for the enzyme functioning. It was concluded that the resistance of Mesembryanthemum crystallinum, a halophyte, to excess cadmium content in the medium was achieved by its predominant accumulation in roots, where excess cadmium is compartmentalized in the apoplast and seems to be subjected to detoxification through pectate formation. Moreover, the leaves and, particularly, the roots are characterized by a high activity of the antioxidant systems, such as guaiacol-dependent peroxidases, and an occurrence of proline at modest cadmium concentrations.     

干旱及镉污染对巨菌草生理和镉富集特征的影响

巨菌草因具有生长迅速、生物量大等优点而成为重金属污染修复的良好材料,干旱是影响其生长和修复能力的主要原因。该研究采用盆栽实验方法,探讨了干旱处理(25%土壤田间持水量)、镉处理(3mg·kg~(-1))及其交互处理对巨菌草生长、光合、抗氧化酶活性、活性氧含量、镉积累与分配特征的影响。结果表明:(1)与对照相比,干旱处理、镉处理及其交互处理对巨菌草生物量积累和光合作用均有一定抑制作用,但各处理巨菌草的耐性系数均较高;叶片中丙二醛(MDA)含量及过氧化物酶(POD)和过氧化氢酶(CAT)活性在各处理下均不同程度升高,抗坏血酸过氧化物酶(APX)活性在交互处理下显著升高,而超氧化物歧化酶(SOD)活性在镉处理和交互处理下显著降低。(2)与单一处理相比,无论从生物量积累,还是叶片活性氧引起的细胞膜受损伤程度(用MDA表示)来看,交互处理并没有引起更严重的负面效应。(3)镉和交互处理下巨菌草各器官的镉含量均显著增加,且主要积累在根部;与镉处理相比,交互处理显著降低巨菌草的镉富集量,但未显著降低其地上部镉富集量。研究发现,巨菌草具有较强的耐旱性和抗镉污染的能力,干旱与镉交互处理并不会造成更严重的叠加负面影响,但会显著降低巨菌草地下部的镉富集量;在受到干旱及镉污染交互影响的区域种植巨菌草具有良好的修复前景。     

Cadmium and mitochondria

The heavy metal cadmium (Cd) a pollutant associated with several modern industrial processes, is absorbed in significant quantities from cigarette smoke, water, food and air contaminations.It is known to have numerous undesirable effects on health in both experimental animals and humans, targeting kidney, liver and vascular system.The molecular mechanism accounting for most of the biological effects of Cd are not well-understood and the toxicity targets are largely unidentified.The present review focuses on important recent advances about the effects of cadmium on mitochondria of mammalian cells.Mitochondria are the proverbial powerhouses of the cell, running the fundamental biochemical processes that produce energy from nutrients using oxygen. They are among the key intracellular targets for different stressors including Cd.This review provides new additional informations on the cellular and molecular aspects of the interaction between Cd and cells, emphasizing alterations of mitochondria as important events in Cd cytotoxicity, thus representing an important basis for understanding the mechanisms of cadmium effect on the cells.     

Cadmium inhibits the functions of eukaryotic MutS complexes

Exposure of yeast cells to low concentrations of cadmium results in elevated mutation rates due to loss of mismatch repair (MMR), and cadmium inhibits MMR activity in extracts of human cells. Here we show that cadmium inhibits both Msh2-Msh6- and Msh2-Msh3-dependent human MMR activity in vitro. This inhibition, which occurs at a step or steps preceding repair DNA synthesis, is observed for repair directed by either a 3' or a 5' nick. In an attempt to identify the protein target(s) of cadmium inhibition, we show that cadmium inhibition of MMR is not reversed by addition of zinc to the repair reaction, suggesting that the target is not a zinc metalloprotein. We then show that cadmium inhibits ATP hydrolysis by yeast Msh2-Msh6 but has no effect on ATPase hydrolysis by yeast Mlh1-Pms1. Steady state kinetic analysis with wild type Msh2-Msh6, and with heterodimers containing subunit-specific Glu to Ala replacements inferred to inactivate the ATPase activity of either Msh2 or Msh6, suggest that cadmium inhibits ATP hydrolysis by Msh6 but not Msh2. Cadmium also reduces DNA binding by Msh2-Msh6 and more so for mismatched than matched duplexes. These data indicate that eukaryotic Msh2-Msh3 and Msh2-Msh6 complexes are targets for inhibition of MMR by cadmium, a human lung carcinogen that is ubiquitous in the environment.     

Cadmium accumulation in the chloroplast of Euglena gracilis

Intracellular distribution of Cd, cysteine, glutathione, and Cd-induced thiol peptides in Euglena gracilis cultured under photoheterotrophic conditions was studied. After 3 days of culture with 0.2 m M CdCl₂, 62% of the Cd accumulated by cells was equally distributed between the cytosolic and chloroplastic fractions. However, after 8 days, metal content increased in the crude chloroplastic fraction to 40% of total and decreased to 19% in the cytosol; in Percoll-purified chloroplasts the estimated content of Cd raised to 62%. Accumulation of Cd in chloroplasts could be mediated by a transporter of free Cd²⁺, since uptake of added CdCl₂ in isolated chloroplasts exhibited a hyperbolic type of kinetics with a K_m of 57 µ M and V_max of 3.7 nmol (mg protein)⁻¹ min⁻¹. The contents of cysteine and glutathione markedly increased in both chloroplasts (7–19 times) and cytosol (4–9 times) by exposure to Cd²⁺, although they were always higher in the cytosol. Thiol-containing peptides induced by Cd were mainly located in the cytosol after 3 days, and in the chloroplasts after 8 days of culture. The data suggested that Cd was compartmentalized into chloroplasts in a process that may involve the transport of free Cd and the participation of thiol-peptides.     

镉胁迫下硫素对嗜鱼外瓶霉生长、矿质元素与镉含量的影响

镉(100 mg/L)胁迫下,研究不同浓度硫素(硫离子)对深色有隔内生真菌(Dark septate endophyte,DSE)——嗜鱼外瓶霉(Exophiala pinsciphila)菌株生长、矿质元素(钙、镁、氮、磷、硫)与镉含量的影响.结果表明:在100 mg/L镉胁迫下,低浓度(0.06和0.30 mmol...     

Cadmium uptake by crops from the subsoil

Plant roots penetrate into the subsoil from which they may take up heavy metals, resulting in accumulation in the plant. The subsoil may contain heavy metals, possibly as a result of ploughing down contaminated topsoil. This is why the effect of Cd in the subsoil on Cd plant uptake was studied in outdoor miniplots in eight consecutive years. Cd (as Cd(NO3)2.4H2O) was added to four different layers of two soils (a sand and a sandy loam) at the start of the experiment. Nine arable and vegetable crops were grown and analysed for Cd. For most investigated crops Cd uptake increased linearly with increasing depth of Cd addition to the soils and for some crops (spinach and potato) the increase was exponential (decreasing increase). Cd uptake by crops on sand was higher than on sandy loam. As most investigated crops accumulated Cd from the subsoil, ploughing down a Cd-contaminated topsoil into the subsoil is a risk for the safe production of food and feed crops. It is concluded that acceptable Cd concentration levels in soils should not only be based an the Cd concentration in the topsoil but also on that in the rooted subsoil.     

Effects of Bacteria on Cadmium Bioaccumulation in the Cadmium Hyperaccumulator Plant Beta Vulgaris Var. Cicla L.

To investigate the effects of two cadmium-tolerant bacteria, Staphylococcus pasteuri (S. pasteuri X1) and Agrobacterium tumefaciens (A. tumefaciens X2), on cadmium uptake by the cadmium hyperaccumulator plant Beta vulgaris var. cicla L., a pot experiment with artificially contaminated soil was conducted. The results demonstrated that both cadmium-tolerant bacteria enhanced the dry weight of Beta vulgaris var. cicla L. The total dry weights of plants in the control CK20, S. pasteuri X1 and A. tumefaciens X2 treatments were 0.85, 1.13, and 1.38 g/pot, respectively. Compared with the control CK20 findings, the total dry weight of plants was increased by 32.8 and 61.1% after inoculation with S. pasteuri X1 and A. tumefaciens X2, respectively, indicating that A. tumefaciens X2 more strongly promoted the growth of Beta vulgaris var. cicla L. than S. pasteuri X1. In addition, inoculation with S. pasteuri X1 and A. tumefaciens X2 significantly (p < 0.05) promoted cadmium uptake by plants and improved the bioaccumulation of cadmium by the plants from the soil. Moreover, the inoculation of S. pasteuri X1 and A. tumefaciens X2 effectively facilitated the transfer of cadmium in the soil from the Fe-Mn oxide and residual fractions to the soluble plus exchangeable and weakly specially adsorbed fractions in the rhizosphere soils of plants. The bacterial enhancement of cadmium phytoavailability might provide a potential and promising method to increase the efficiency of phytoextraction.     

木槿品种对镉胁迫的生理响应及耐镉能力评价

研究镉胁迫对木槿的生理影响,比较木槿品种的镉耐受能力,为镉污染地区的植物材料选择提供依据.以3个木槿品种为材料,采取盆栽控制试验,测定其生长、生理指标,通过隶属函数分析综合比较品种耐镉能力.木槿的株高与地径增长量、叶绿素A+B与可溶性蛋白含量随胁迫浓度增加呈先上升后降低或逐渐降低趋势,而且随时间延长,降低程度不断加强;...     

南瓜对镉的吸收积累特性研究

对南瓜进行盆栽试验,通过加入不同含量的镉、CaCO₃和草炭土,研究南瓜对镉的吸收积累特性,利用火焰原子吸收法测定。结果表明,南瓜植株对镉的富集量主要集中在茎、根中;当土壤镉含量小于5mg·kg^-1时,对南瓜根的生长有促进作用,当土壤镉含量大于5mg·kg^-1时,开始对根的生长产生抑制作用,抑制作用随镉含量的增大而加强;在土壤中施CaCO₃,能降低南瓜对镉的吸收;在土壤中加入草炭土,在一定范围内,它能促进南瓜对镉的吸收。     

Cadmium carcinogenesis in review

Cadmium is an inorganic toxicant of great environmental and occupational concern which was classified as a human carcinogen in 1993. Occupational cadmium exposure is associated with lung cancer in humans. Cadmium exposure has also, on occasion, been linked to human prostate cancer. The epidemiological data linking cadmium and pulmonary cancer are much stronger than for prostatic cancer. Other target sites for cadmium carcinogenesis in humans (liver, kidney, stomach) are considered equivocal. In rodents, cadmium causes tumors at several sites and by various routes. Cadmium inhalation in rats results in pulmonary adenocarcinomas, supporting a role in human lung cancer. Prostate tumors and preneoplastic proliferative lesions can be induced in rats after cadmium ingestion or injection. Prostatic carcinogenesis in rats occurs only at cadmium doses below those that induce chronic degeneration and dysfunction of the testes, a well-known effect of cadmium, confirming the androgen dependency of prostate tumors. Other targets of cadmium in rodents include the testes, adrenals, injection sites, and hematopoietic system. Various treatments can modify cadmium carcinogenesis including supplemental zinc, which prevents cadmium-induced injection site and testicular tumors while facilitating prostatic tumors. Cadmium is poorly mutagenic and probably acts through indirect mechanisms, although the precise mechanisms remain unknown.     

Cadmium toxicity in fishes

Cadmium from industrial effluents pollutes sea and river water and hence may effect the fish population therein. The present investigation shows that resistivity is greater in case of air-breathing fishes as compared to non air-breathing fishes with regards to their duration of survival and growth when exposed to a cadmium containing environment. Under sub-acute levels of cadmium exposure, they respond differently so far as the activities of their liver, gill and intestinal lysosomal enzymes are concerned. Though both species show a definite stress condition on cadmium exposure, the two anatomically different fishes respond differently towards carbohydrate metabolism as observed from liver and muscle glycogen content, liver microsomal glucose-6-phosphatase activity and serum glucose level.     

Cadmium accumulation in tissues of the mussel Mytilus galloprovincialis

Studies have been made on cadmium accumulation in tissues of mussels kept within 20-60 days in water artificially enriched by Cd up to 20-100 micrograms/l. Irrespectively of cadmium concentration in the medium, its accumulation in tissues decreases in the following order: mid-gut gland, gills, gonads, mantle, adductor. Maximum concentration of Cd was found in the digestive tubuli of the mid-gut gland by X-ray microanalysis. The increase in S and, to a lower extent, P concentrations in these tubuli was also observed. It is suggested that the latter is due to immobilization of Cd by metal-binding proteins as well as to lyzosomal vesicles involved into detoxication of Cd. The increase in the external cadmium up to 100 micrograms/l did not affect the level of K, Ca and Mg in tissues of the mussel.     

Cadmium detoxification in protists

Studies on cadmium (Cd) detoxification mechanisms mostly concern multicellular organisms, while information on eukaryotic unicellular organisms such as protists is very scanty. This study focuses on these organisms, and deals with the response of some species of ciliates to a non-essential metal like Cd. The effect of accumulation and tolerance are reported for Tetrahymena pyriformis T. pigmentosa and T. thermophila, and for three species of Hypotrichida. Cd is bound to both particulate and soluble fractions. These two compartments, which play an important role in intracellular metal homeostasis, are different in the species considered. In Hypotrichida, the particulate compartment binds Cd very promptly, while it is still present often three days of treatment in the soluble fraction of Tetrahymena. Two Cd-Zn binding isothioneins were isolated from the soluble fraction of T. pyriformis and T. pigmentosa. The primary structure revealed that the equivalent proteins from the two species have identical sequences and that the two isoforms differ only in the presence or absence of a lysine residue at the N-terminus. These metallothioneins are unusually long and have a unique internal homology which suggests that the proteins originate by gene duplication. The chains contain 331 cysteine residues, 16 of which are arranged in unique repeating motifs. The similarities of protist metallothioneins with other eukaryotic metallothioneins are discussed.     

Closing the Loop on Cadmium - An Assessment of the Material Cycle of Cadmium in the U.S. (11 pp)

Goal, Scope and Background In this study, the major flows of cadmium in the U.S. economy are quantified and the primary sinks are identified to gauge the need for additional policy to minimize the potential human health and ecosystem risks associated with these flows. Because of the concurrent occurrence of cadmium and zinc in ore, we also consider the relevant portions of the material cycle of zinc. Methods We estimated the flows of cadmium through U.S. manufacturing using a mass balance approach with data provided by the U.S. Geological Survey's Minerals Yearbook. Cadmium emissions factors were created using facility specific information found in the U.S. Toxics Release Inventory and were used to model future losses. Data gaps were filled through review of relevant literature. We modeled the import and sales of nickel-cadmium batteries with rechargeable battery usage trends and estimates of market share by battery chemistry. Results and Conclusion Primary cadmium in the U.S. is almost exclusively produced as a co-product of zinc. Almost all zinc and cadmium mined in the U.S. is exported to foreign smelters as ore concentrate. We estimate that the bulk of cadmium consumed in the U.S. economy (~90%) is imported in the form of nickel-cadmium rechargeable batteries. These batteries can be divided into the larger wet-cells and portable rechargeable batteries (PRB). The collection rate for the recycling of large wet cells was found to be high (80%) while the collection rate for PRBs is low (5-20%). The Rechargeable Battery Recycling Corporation (RBRC) is responsible for the collection of these batteries which are recycled exclusively by the International Materials Reclamation Company (INMETCO). The remaining PRBs are generally disposed of in municipal solid waste (MSW) landfills. This study provides a detailed substance flow analysis of U.S. stocks and flows of cadmium in products, however additional research is needed to better quantify the associated exposures and risks. Recommendation and Perspective Based on our analysis, we make four recommendations. First we suggest that if cadmium is to be used, it should be used in long-lived products that can be easily collected and recycled with minimal losses. Second, continued cadmium use should be coupled with renewed efforts on the part of policy-makers to encourage the collection and recycling of cadmium-bearing products. At present, consumers do not see the environmental cost associated with the proper disposal of the cadmium content of NiCd batteries. Policy options for improving recycling rates include collecting deposits and providing rewards for the return of spent batteries, taxing or otherwise discouraging discarding PRBs in municipal solid waste, and providing incentives for extended producer responsibility. Third, we highlight the importance of the connection between zinc mining and the supply of cadmium in designing an effective policy to manage the risks associated with cadmium. Fourth, we recommend that policy measures be taken to provide the necessary data required to improve our understanding of the flow of cadmium into the U.S. in the form of product imports and the amount of cadmium lost or disposed of by recycling processes.