Chromium and genomic stability

Many metals serve as micronutrients which protect against genomic instability. Chromium is most abundant in its trivalent and hexavalent forms. Trivalent chromium has historically been considered an essential element, though recent data indicate that while it can have pharmacological effects and value, it is not essential. There is no data indicating that trivalent chromium promotes genomic stability and, instead may promote genomic instability. Hexavalent chromium is widely accepted as highly toxic and carcinogenic with no nutritional value. Recent data indicate that it causes genomic instability and also has no role in promoting genomic stability.     

Elucidation of the percutaneous absorption of chromium compounds by functional proteomics

Chromium compounds are known to be associated with cytotoxicity and carcinogenicity when applied via a skin route. The aim of this study was to evaluate the skin permeability and toxicological profiles of four chromium species. Chromium permeation across the skin, as determined by an in vitro Franz cell, decreased in the order of sodium chromate>potassium chromate>potassium dichromate>chromium nitrate. The uptake of chromium species within the skin generally showed a contrary trend to the results of permeation, although differences among the various compounds were not large. Levels of in vivo skin deposition of the four compounds showed no statistically significant differences. Potassium chromate produced the greatest disruption of the skin structure as determined by HE staining, followed in order by sodium chromate, potassium dichromate, and chromium nitrate. This indicates that hexavalent chromium elicited greater toxicity to the skin compared to trivalent chromium. A similar result was observed for the viability of skin fibroblasts. To improve our understanding of the molecular mechanisms leading to functional changes in proteins, proteomic tools, including 2‐DE and MS techniques combined with sequence database correlations, were applied to identify target proteins altered by pathologic states. Eight protein spots, corresponding to cutaneous enzymes involved in energy metabolism and chaperon proteins, which were identified and discussed in this study, were associated with skin cytotoxicity, immunity, and carcinogenesis. In addition, functional proteomics of skin tissues may provide a promising tool for developing therapeutic strategies and can serve as the basis for further research.     

Potential of Live Spirulina platensis on Biosorption of Hexavalent Chromium and Its Conversion to Trivalent Chromium

Microalga biomass has been described worldwide according their capacity to realize biosorption of toxic metals. Chromium is one of the most toxic metals that could contaminate superficial and underground water. Considering the importance of Spirulina biomass in production of supplements for humans and for animal feed we assessed the biosorption of hexavalent chromium by living Spirulina platensis and its capacity to convert hexavalent chromium to trivalent chromium, less toxic, through its metabolism during growth. The active biomass was grown in Zarrouk medium diluted to 50% with distilled water, keeping the experiments under controlled conditions of aeration, temperature of 30°C and lighting of 1,800 lux. Hexavalent chromium was added using a potassium dichromate solution in fed-batch mode with the aim of evaluate the effect of several additions contaminant in the kinetic parameters of the culture. Cell growth was affected by the presence of chromium added at the beginning of cultures, and the best growth rates were obtained at lower metal concentrations in the medium. The biomass removed until 65.2% of hexavalent chromium added to the media, being 90.4% converted into trivalent chromium in the media and 9.6% retained in the biomass as trivalent chromium (0.931 mg.g^?1).     

Functional proteomics reveals hepatotoxicity and the molecular mechanisms of different forms of chromium delivered by skin administration

Chromium compounds are known to be associated with cytotoxicity and carcinogenicity when applied via the skin. However, there is no perspective research to elucidate the causations between chromium exposure and hepatotoxicity. In the present study, the impact of hexavalent/trivalent chromium on the liver and the underlying pathogenic processes were revealed in the female nude mice model. The liver damage under different treatments was evaluated by histologic examination. Functional proteome tools combined with a network analysis revealed statistically significant candidate protein networks predicted to be changed in the presence of chromium compounds. RNA interference-mediated silencing and immunohistochemistry were used to confirm whether the candidate protein was capable of resulting in hepatotoxicity elicited by chromium. Potassium chromate as the Cr(VI) compound generated greater oxidative stress, apoptosis and hepatotoxicity compared to chromium nitrate [Cr(III)]-treated samples. The most meaningful changes were observed amongst proteins involved in carbohydrate metabolism, endoplasmic reticulum (ER) stress, calcium homeostasis and apoptosis. Furthermore, abrogation of transitional ER ATPase (VCP) led to significant inhibition in hepatic cell viability under Cr(VI) administration, and the expression profiles of cytokeratin were closely correlated with apoptotic degrees of liver tissue. Collectively, our findings suggest that Cr(VI) might induce the accumulation of misfolded proteins and adverse effects leading to cell apoptosis and liver injury. These signature networks represent an approach to discover novel relationships in complex data, and functional proteomics of liver may provide solid evidence of chromium-caused hepatic damage via the skin.     

Role of physiological antioxidants in chromium(VI)-induced cellular injury.

Chromium(VI) compounds are well known to be potent toxic and carcinogenic agents. Because chromium(VI) is easily taken up by cells and is subsequently reduced to the trivalent form, the formation of chromium(III) or other intermediate oxidation states such as chromium(V) and (IV) is believed to play a role in the adverse biological effects of chromium(VI) compounds. Recent in vitro studies have shown that this reduction process generates free radical species such as active oxygen radicals. Furthermore, physiological antioxidants are reported to modify the genotoxic and toxic effects of chromate. This article reviewed the recent in vitro and in vivo studies of the effects of antioxidants including active oxygen scavengers; glutathione; vitamins B2, E, and C, on chromate-induced injury such as DNA lesions; lipid peroxidation; enzyme inhibition; cytotoxicity; mutation; and so on. In addition, the mechanism of action of these antioxidants was discussed with respect to the formation of active oxygen radicals and paramagnetic chromium such as chromium(V) and (III). Such studies may help elucidate the mechanism of chromium(VI) toxicity as well as the mechanism of protection.     

Effect of chromium on growth of Pseudomonas aeruginosa

Tolerance level to trivalent chromium-Cr(salen)(H2O)2+ and hexavalent chromium-K2Cr2O7 was assessed in P. aeruginosa isolated from tannery effluent soil. It could tolerate 80 and 100 ppm in liquid cultures and up to 100 and 200 ppm in plate count agar in the presence of trivalent and hexavalent chromium respectively. Unadapted cells took a longer time to grow than adapted cells in the presence of K2Cr2O7. Chromium influenced the cellular contents, morphology and respiration of P. aeruginosa. The chosen trivalent salt of chromium was more toxic than the hexavalent one.     

Interactions of chromium with microorganisms and plants

Chromium is a highly toxic non-essential metal for microorganisms and plants. Due to its widespread industrial use, chromium (Cr) has become a serious pollutant in diverse environmental settings. The hexavalent form of the metal, Cr(VI), is considered a more toxic species than the relatively innocuous and less mobile Cr(III) form. The presence of Cr in the environment has selected microbial and plant variants able to tolerate high levels of Cr compounds. The diverse Cr-resistance mechanisms displayed by microorganisms, and probably by plants, include biosorption, diminished accumulation, precipitation, reduction of Cr(VI) to Cr(III), and chromate efflux. Some of these systems have been proposed as potential biotechnological tools for the bioremediation of Cr pollution. In this review we summarize the interactions of bacteria, algae, fungi and plants with Cr and its compounds.     

Toxicity and mutagenicity of hexavalent chromium on Salmonella typhimurium.

Four hexavalent and two trivalent chromium compounds were tested for toxicity and mutagenicity by means of the Salmonella typhimurium/mammalian-microsome test. All hexavalent compounds yielded a complete inhibition of bacterial growth at doses of 400 to 800 mug/plate, a significant increase of his(+) revertant colonies at doses ranging from 10 to 200 mug, and no effect at doses of less than 10 mug. The distinctive sensitivity of the four Salmonella strains tested (TA1535, TA1537, TA98, and TA100) suggested that hexavalent chromium directly interacts with bacterial deoxyribonucleic acid by causing both frameshift mutations and basepair substitutions. The latter mutations, which are prevalent, are amplified by an error-prone recombinational repair of the damaged deoxyribonucleic acid. On the average, 1 mumol of hexavalent chromium yielded approximately 500 revertants of the TA100 strain, irrespective of the compound tested (sodium dichromate, calcium chromate, potassium chromate, or chromic acid). The mutagenic potency of the hexavalent metal was not enhanced by adding the microsomal fraction of rat hepatocytes, induced either with sodium barbital or with Aroclor 1254. The two trivalent compounds (chromium potassium sulfate and chromic chloride), with or without the microsomal fraction, were neither toxic nor mutagenic for the bacterial tester strains.     

Effect of hexavalent carcinogenic chromium on carp Cyprinus carpio immune cells

Chromium is widely used in industrial processes, and is released into aquatic environments by electroplating, tannery and textile industries. Fishes in natural waters or in aquaculture facilities supplied with these waters are exposed to chromium waste and are presumed to be affected by deposits. Herein, we examine the effect of hexavalent chromium on carp Cyprinus carpio derived immune cells. In vitro exposure of carp leukocytes to hexavalent chromium induced cytotoxicity, decreased mitogen-induced lymphocyte activation and phagocyte functions at concentrations between 2 and 200 micromol Cr l(-1). Neutrophils responded to chromium challenge by changes in cell shape together with reduced nitric oxide and reactive oxygen production. This occurred at much lower concentrations than for the cytotoxic effects seen in leukocyte cultures derived from peripheral blood or pronephros. In a similar way, activation of carp lymphocytes by pokeweed mitogen was reduced in a dose-dependent manner, while cytotoxic effects on non-activated lymphocytes were observed at much higher doses of 200 micromol Cr l(-1). Altered lymphocyte and neutrophil functions are considered to be responsible for decreased resistance to pathogens observed in fishes under chronic chromium challenge.     

Oxidation of inactive trivalent chromium to the mutagenic hexavalent form.

Soluble trivalent chromium compounds (chromium potassium sulfate, chromium nitrate, chromium chloride, neochromium and chromium alum) were inactive for Salmonella typhimurium TA100, even at milligram amounts per plate. No effect could be detected either in the absence or in the presence of rat-liver, lung or muscle microsomal fractions, of rat-muscle mitochondria (with or without ATP), of oxidized glutathione (GSSG), or of human serum, plasma or erythrocyte lysates. Conversely, addition of a strongly oxidizing agent (potassium permanganate) resulted in toxic effects in plates incorporating more than 40--80 microgram of compounds and elicited a dose-effect mutagenic response at 10--40 microgram per plate. These effects could be ascribed to oxidation of chromium from the trivalent to the active hexavalent state. Insoluble chromite, as tested in the spot test, was spontaneously mutagenic, owing to contamination of the industrial product with hexavalent chromium. The results obtained may be useful to interpret the findings of carcinogenicity tests and to predict health hazards linked to chromium.     

Chromium in the environment: factors affecting biological remediation

Chromium, in the trivalent form (Cr(III)), is an important component of a balanced human and animal diet and its deficiency causes disturbance to the glucose and lipids metabolism in humans and animals. In contrast, hexavalent Cr (Cr(VI)) is highly toxic carcinogen and may cause death to animals and humans if ingested in large doses. Recently, concern about Cr as an environmental pollutant has been escalating due to its build up to toxic levels in the environment as a result of various industrial and agricultural activities. In this review, we present the state of knowledge about chromium mobility and distribution in the environment and the physiological responses of plants to Cr with the desire to understand how these processes influence our ability to use low cost, environmentally friendly biological remediation technologies to clean up Cr-contaminated soils, sediments, and waters. The use of biological remediation technologies such as bioremediation and phytoremediation for the cleanup of Cr-contaminated areas has received increasing interest from researchers worldwide. Several methods have been suggested and experimentally tested with varying degrees of success.     

Bacterial interactions with chromate

Hexavalent chromium compounds (chromates and dichromates) are highly toxic and are considered as mutagens and carcinogens. These compounds are discharged frequently to the environment as a result of diverse industrial processes. Some microorganisms are able to reduce hexavalent chromium to the less toxic trivalent form. Chromate pollution has promoted the selection of bacterial strains possessing chromate resistance determinants, usually carried by plasmids. Strains combining both abilities, i.e. resistance to and reduction of chromate, are potentially useful for detoxifying chromate polluted waste waters.     

Studies on the uptake of trivalent and hexavelent chromium by onion (Allium cepa)

Abstract

Experiments were conducted to examine the uptake and translocation of root-absorbed trivalent and hexavalent state of chromium in the onion plant (Allium cepa) grown in soil and sand culture. Chromium content in plant tissues increased with increasing amount of added chromium. Distribution of chromium in the plant in general, found to be in the order: root>>bulb>shoot. Higher uptake in the plants grown in sand from both the sources of chromium was observed as compared with the corresponding values for soil culture. Morphological and growth effects of the treatments of different oxidation state of chromium indicated that higher doses of Cr(VI) [150 and 300 μg mL^?1] were more toxic to the onion plants compared to equivalent doses of Cr(III).     

Toxicity and Mutagenicity of Hexavalent Chromium on Salmonella typhimurium

Four hexavalent and two trivalent chromium compounds were tested for toxicity and mutagenicity by means of the Salmonella typhimurium/mammalian-microsome test. All hexavalent compounds yielded a complete inhibition of bacterial growth at doses of 400 to 800 μg/plate, a significant increase of his⁺ revertant colonies at doses ranging from 10 to 200 μg, and no effect at doses of less than 10 μg. The distinctive sensitivity of the four Salmonella strains tested (TA1535, TA1537, TA98, and TA100) suggested that hexavalent chromium directly interacts with bacterial deoxyribonucleic acid by causing both frameshift mutations and basepair substitutions. The latter mutations, which are prevalent, are amplified by an error-prone recombinational repair of the damaged deoxyribonucleic acid. On the average, 1 μmol of hexavalent chromium yielded approximately 500 revertants of the TA100 strain, irrespective of the compound tested (sodium dichromate, calcium chromate, potassium chromate, or chromic acid). The mutagenic potency of the hexavalent metal was not enhanced by adding the microsomal fraction of rat hepatocytes, induced either with sodium barbital or with Aroclor 1254. The two trivalent compounds (chromium potassium sulfate and chromic chloride), with or without the microsomal fraction, were neither toxic nor mutagenic for the bacterial tester strains.     

Hexavalent chromium reduction by bacteria from tannery effluent

Chromium is generated from several industrial processes. It occurs in different oxidation states, but Cr(III) and Cr(VI) are the most common ones. Cr(VI) is a toxic, soluble environmental contaminant. Some bacteria are able to reduce hexavalent chromium to the insoluble and less toxic Cr(III), and thus chromate bioremediation is of considerable interest. An indigenous chromium-reducing bacterial strain, Rb-2, isolated from a tannery water sample, was identified as Ochrobactrum intermedium, on the basis of 16S rRNA gene sequencing. The influence of factors like temperature of incubation, initial concentration of Cr, mobility of bacteria, and different carbon sources were studied to test the ability of the bacterium to reduce Cr(VI) under variable environmental conditions. The ability of the bacterial strain to reduce hexavalent chromium in artificial and industrial sewage water was evaluated. It was observed that the mechanism of resistance to metal was not due to the change in the permeability barrier of the cell membrane, and the enzyme activity was found to be inductive. Intracellular reduction of Cr(VI) was proven by reductase assay using cell-free extract. Scanning electron microscopy revealed chromium precipitates on bacterial cell surfaces, and transmission electron microscopy showed the outer as well as inner distribution of Cr(VI). This bacterial strain can be useful for Cr(VI) detoxification under a wide range of environmental conditions.     

The Effect of Chromium on the Photosynthesis and Growth of Diatoms and Green Algae

The effect of hexavalent chromium ions on the photosynthesis and growth of the diatom Nitzschia palea and the green alga Chlorella pyrenoidosa has been studied and compared with the effect of Cu and Hg. The effect of chromium is very similar to that of Cu and Hg, but it is more than one hundred times less toxic for the algae than copper. The toxicity of chromium is not counteracted by adding Fe to the culture solution. The problems regarding cleaning glass-ware in dichromate-sulphuric acid are discussed and it is strongly recommended to use other cleaning agents.     

Hexavalent Chromium Reduction in Soils Contaminated with Chromated Copper Arsenate Preservative

The toxicity and mobility of chromium in the environment greatly depends upon its speciation. The reduction of hexavalent chromium to trivalent chromium in a soil environment was examined by spiking three soil types (sandy, clayey, and organic soils) with a common wood preservative solution known as chromated copper arsenate (CCA). Chromium in the CCA preservative solution exists in the hexavalent form. The total and hexavalent chromium concentrations (mg/kg) were measured over a period of 11 months. Leachable chromium concentrations (mg/L) were assessed using the synthetic precipitation leaching procedure (SPLP). The degree and rate of hexavalent chromium reduction were similar for the sand and clayey soil, but much greater for the organic soil. Most of the chromium reduction occurred within the first month of the experiment. At the end of the experiment, approximately 50% of the hexavalent chromium was converted to the trivalent form in the sand and clayey soils. Hexavalent chromium concentrations were below detection in the organic soil at the end of the experiment. Nearly all of the chromium observed in the SPLP leachates was in the form of hexavalent chromium. Chromium leaching was thus greatest in the sand and clay soils where the hexavalent chromium persisted. The results indicate that hexavalent chromium in soils can persist for considerable time periods, in particular in soils with low organic matter content.

     

Is chromium a trace essential metal?

If chromium is an essential metal it must have a specific role in an enzyme or cofactor, and a deficiency should produce a disease or impairment of function. To date, no chromium-containing glucose tolerance factor has been characterized, the purpose of the low-molecular-weight chromium-binding protein is questionable, and no direct interaction between chromium and insulin has been found. Furthermore, chromium3+ is treated like the toxic metals arsenic, cadmium, lead and mercury in animals. Chromium3+ may be involved in chromium6+-induced cancers because chromium6+ is converted to chromium3+ in vivo, and chromium3+ is genotoxic and mutagenic. Although there is no direct evidence of chromium deficiencies in humans, dietary supplements exist to provide supraphysiological doses of absorbable chromium3+. Chromium3+ may act clinically by interfering with iron absorption, decreasing the high iron stores that are linked to diabetes and heart disease. If so, this would make chromium3+ a pharmacological agent, not an essential metal.     

Hexavalent chromium is cytotoxic and genotoxic to the North Atlantic right whale (Eubalaena glacialis) lung and testes fibroblasts

Although hexavalent chromium is a known genotoxic agent in human and terrestrial mammals and is present in seawater and air, its effects on marine mammals including the endangered North Atlantic right whale are unknown and untested. The present study investigated the cytotoxic and genotoxic effects of hexavalent chromium in primary cultured North Atlantic right whale lung and testes fibroblasts and levels of total chromium in skin biopsies from North Atlantic right whales. Cytotoxicity was measured by clonogenic survival assay. Genotoxicity was measured as production of chromosome aberrations. Tissue chromium levels were determined from skin biopsies of healthy free-ranging whales in the Bay of Fundy using inductively coupled plasma optical emission spectroscopy. Hexavalent chromium-induced concentration-dependent increases in right whale lung and testes fibroblast cytotoxicity with the testes more sensitive to the cytotoxic effects. It also induced concentration-dependent increases in chromosomal aberrations in both cell types with no significant difference in sensitivity. Skin biopsy data indicate that North Atlantic right whales are exposed to chromium and accumulate a range of 4.9-10 microg Cr/g tissue with a mean of 7.1 microg/g. Hexavalent chromium is cytotoxic and genotoxic to North Atlantic right whale cells. The whales have tissue chromium levels that are concerning. These data support a hypothesis that chromium may be a concern for the health of the North Atlantic right whales. Considering these data with chromium chemistry, whale physiology and atmospheric chromium levels further suggest that inhalation may be an important exposure route.     

Genotoxicity of Tri- and Hexavalent Chromium Compounds In Vivo and Their Modes of Action on DNA Damage In Vitro

Chromium occurs mostly in tri- and hexavalent states in the environment. Hexavalent chromium [Cr(VI)] compounds are extensively used in diverse industries, and trivalent chromium [Cr(III)] salts are used as micronutrients and dietary supplements. In the present work, we report that they both induce genetic mutations in yeast cells. They both also cause DNA damage in both yeast and Jurkat cells and the effect of Cr(III) is greater than that of Cr(VI). We further show that Cr(III) and Cr(VI) cause DNA damage through different mechanisms. Cr(VI) intercalates DNA and Cr(III) interferes base pair stacking. Based on our results, we conclude that Cr(III) can directly cause genotoxicity in vivo.