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Effects of chromium(III) on DNA replication in vitro.

A number of metal compounds are important environmental carcinogens; however, the molecular mechanisms of metal-induced genotoxicity are not yet understood. Chromium, for example, is substantially mutagenic in vivo and has been shown to decrease the DNA replication fidelity in vitro. But the mechanism of chromium-induced mutagenesis is unknown and the role of replication fidelity in chromium-induced carcinogenesis is unclear. We have used in vitro DNA replication assays to investigate the effects of chromium ions on DNA polymerase activity preliminary to studying their role in chromium-induced mutagenesis. Biologically active M13mp2 DNA was replicated with purified DNA polymerases in the presence of micromolar amounts of chromium with or without the normal divalent cation, magnesium. Nucleotide incorporation kinetics were determined and sequence specific pausing was analyzed by primer-extension. Our results have demonstrated an unexpected polymerase activation by low (0.5-5.0 microns) concentrations of chromium (III), although higher concentrations of chromium are increasingly inhibitory. The increased incorporation seem at low chromium(III) concentrations is the result of increased enzyme processivity and is not polymerase specific. The possible relationship between processivity and metal-ion mutagenesis is discussed.

Chromium↗

Bacterial removal of chromium (VI) and (III) in a continuous system.

The capacity of Acidithiobacillus ferrooxidans and Acidithiobacillus thiooxidans to reduce different concentrations of hexavalent chromium in shake flask cultures has been investigated. A. ferrooxidans reduces 100% of chromium (VI) at concentrations of 1, 2.5 and 5 ppm, but in the presence of 10 ppm only 42.9% of chromium (VI) was reduced after 11 days of incubation. A. thiooxidans showed a lower capacity to reduce this ion and total reduction of chromium (VI) was only obtained for concentrations of 1 and 2.5 ppm, whereas 64.7% and 30.5% was reached for 5 and 10 ppm, respectively, after 11 days. A continuous flow mode system was subsequently investigated, in which A. thiooxidans was immobilized on elemental sulphur and the acidic medium obtained was employed to solubilize chromium (III) and to reduce chromium (VI) present in a real electroplating waste [30% of chromium (III) and 0.1% of chromium (VI)]. The system enabled the reduction of 92.7% of hexavalent chromium and represents a promising way to treat this type of waste in the industry.

Acidithiobacillus↗

Immunomodulatory effects of seabuckthorn (Hippophae rhamnoides L.) against chromium (VI) induced immunosuppression.

The present study reports the immunomodulatory effects of seabuckthorn (Hippophae rhamnoides L.) leaf extract on cellular and humoral immune response by studying delayed-type hypersensitivity response, IL-2, IL-4 and gamma-IFN levels and antibody titres in chromium-induced immunosuppressed animals. Oral feeding of chromium (30 mg/kg bw) significantly inhibited antibody production and S-RBC induced delayed-type hypersensitivity response. Administration of leaf extract (100 mg/kg bw) along with chromium significantly inhibited chromium-induced immunosuppression. To understand the immunomodulatory mechanism of leaf extract, in vitro studies were carried out using rat lymphocytes. Addition of chromium resulted in a significant decrease in lymphocyte size and increased ROS generation. The leaf extract of seabuckthorn significantly inhibited chromium-induced reactive oxygen species (ROS) generation and maintained the cell size identical to that of control cells. Chromium treatment markedly inhibited the mitochondrial transmembrane potential by larger lymphocytes in particular, while the leaf extract restored the same significantly. Chromium also inhibited significantly concanavalin A (ConA) induced IL-2, IL-4 and gamma-IFN production in rat lymphocytes. The leaf extract (100 microg/ml) alone stimulated IL-2 and gamma-IFN production even in the absence of ConA and also inhibited chromium-induced decline in IL-2 and gamma-IFN production but it did not change IL-4 production. These observations suggest that the leaf extract of seabuckthorn has significant immunomodulatory activity and specifically activates the cell-mediated immune response.

Animals↗

Essentiality of chromium in humans.

Chromium is an essential nutrient required for normal sugar and fat metabolism. Insufficient dietary chromium is associated with maturity-onset diabetes and/or cardiovascular diseases. Dietary chromium intake in the U.S. and other developed countries is roughly half of the minimum suggested intake of 50 micrograms. Well controlled studies involving human subjects have demonstrated beneficial effects of supplemental chromium on fasting glucose, glucose tolerance, blood lipids, insulin binding, and hypoglycemic blood glucose values and symptoms. Since chromium is a nutrient and not a therapeutic agent, it will only benefit those people whose signs and symptoms are due to marginal or overt chromium deficiency. Stresses including high sugar diets, strenuous exercise, physical trauma, infection and certain diseases exacerbate the signs and symptoms associated with marginal intakes of dietary chromium. While excessive levels of chromium are usually limited to industrial settings, marginal dietary chromium intake is widespread in the general population and may lead to serious health problems.

Chromium↗

Effects of chromium supplementation on fasting insulin levels and lipid parameters in healthy, non-obese young subjects.

Trivalent chromium is an essential trace element for normal carbohydrate metabolism and insulin sensitivity. Because of this biological activity, chromium supplementation has been studied as a potential therapy of insulin resistant states and dyslipidemias, and has been promoted as a health aid to the general population. To determine if there is a risk of subclinical chromium deficiency in young, otherwise healthy adults, we evaluated the effect of chromium supplementation, versus placebo, on insulin levels and serum lipids in a double-blind, randomized trial in 26 young adults (mean age 36 years). Fasting levels of glucose, immunoreactive insulin (IRI), and lipids (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) were measured before and after 90 days of daily supplementation with a chromium (III)-nicotinate preparation, containing 220 micrograms elemental chromium, or placebo. There were no statistically significant differences in the percentage change of fasting glucose, IRI or lipids between the chromium (n = 15) and placebo (n = 11) groups after 90 days of supplementation. However, those individuals within the chromium group with initial fasting IRI levels greater than 35 pmol/l had a significant decrease in IRI level after supplementation (P < 0.03) despite no significant changes in serum lipids. These subjects may benefit from chromium supplementation by improving insulin sensitivity and cardiovascular risk over time.

Adult↗

Hexavalent chromium produces DNA strand breakage but not unscheduled DNA synthesis at sub-cytotoxic concentrations in hepatocytes.

Rat hepatocytes were used to investigate the possible induction of unscheduled DNA synthesis (UDS) and the extent of DNA strand breaks induced by sodium dichromate (a representative chromium(VI) compound) and chromium acetate hydroxide (chromium(III)) in vitro. Cytotoxicity, measured using tetrazolium salt (MTT) reduction assay, was found at a much higher dose of chromium(III), (> 50 microM), compared to that of chromium(VI), (> 2.5 microM), in cultured hepatocytes over 20 h treatment at 37 degrees C. Chromium(VI), but not chromium(III), stimulated minimal UDS in hepatocytes at sub-cytotoxic concentrations. A positive UDS response was only observed at cytotoxic concentration. DNA strand breaks in hepatocytes were induced by chromium(VI) following incubation at 37 degrees C for 1 h at doses of 10, 20 and 40 microM sodium dichromate. The subsequent ligation of such strand breaks in hepatocytes treated with 40 microM chromium(VI) for 1 h at 37 degrees C was demonstrated. The majority of strand breaks was repaired within 30 min following removal of the chromate. In conclusion, chromate-induced DNA strand breakage, possibly involving the formation of oxygen radicals and lack of significant UDS have some analogy to those produced by ionizing radiation.

Animals↗

Leaching and reduction of chromium in soil as affected by soil organic content and plants.

The oxidation state of chromium in contaminated soils is an important indicator of toxicity and potential mobility. Chromium in the hexavalent state is highly toxic and soluble, whereas the trivalent state is much less toxic and relatively insoluble. A laboratory study investigated the impact of growing plants and supplemental organic matter on chromium transport in soil. Plants alone had no appreciable effect on the chromium oxidation state in soil. Soil columns with higher organic content were associated with lower ratios of chromate:total chromium than the columns with lower organic matter. Analyses of column leachate, plant biomass, and soil indicate that more chromium leaching occurred in the vegetated, low organic columns. Retention of Cr in the soils was correlated to the Cr(III) content. Plant uptake of chromium accounted for less than 1% of the chromium removed from the soil. Overall, the addition of organic matter had the strongest influence on chromium mobility.

Biomass↗

Mutagenicity of chromium picolinate and its components in Salmonella typhimurium and L5178Y mouse lymphoma cells.

Chromium picolinate is one of the most commonly used chromium dietary supplements available in the United States, and it has been marketed to consumers for use in weight loss, increasing muscle mass, and lowering serum cholesterol. Chromium picolinate is a synthetic compound that provides a bioavailable form of Cr(III) that is absorbed better than dietary chromium. However, there are several reports that it can have adverse effects. In order to study the mechanism of observed cellular toxicity and mutagenicity, chromium picolinate and its component compounds, chromium (III) chloride and picolinic acid, were evaluated in Salmonella typhimurium and L5178Y mouse lymphoma cells. Neither chromium picolinate nor chromium chloride induced a mutagenic response in S. typhimurium. However, in the L5178Y mouse lymphoma mutation assay, chromium picolinate induced mutagenic responses without and with the addition of S9.

Animals↗

High-temperature reduction of chromium (VI) in solid alkali.

Chromium (VI) that exists in many industrial wastes is considered highly toxic. One of the most common ways to dispose of these wastes is to reduce chromium (VI) to chromium (III), which is less toxic and can be relatively easily removed or fixed. However, the reduction of chromium (VI) is often conducted in acidic solutions and the chromium (VI) in alkaline solid wastes is hardly to be fully removed. The present study describes a new method for reducing chromium (VI) in alkaline solid. By mixing alkaline solids containing chromium (VI) with an aqueous sucrose solution and then calcinating the resulting mixture at 400-600 degrees C in inertial gas, chromium (VI) can be easily reduced to an insoluble chromium oxide. The reduced fraction can reach up to 99% in 10-20 min under the conditions of temperature above 600 degrees C and sucrose/chromium > or = 1 g/1 g.

Alkalies↗

Activated carbons and low cost adsorbents for remediation of tri- and hexavalent chromium from water.

Hexavalent chromium is a well-known highly toxic metal, considered a priority pollutant. Industrial sources of Cr(VI) include leather tanning, cooling tower blowdown, plating, electroplating, anodizing baths, rinse waters, etc. The most common method applied for chromate control is reduction of Cr(VI) to its trivalent form in acid (pH approximately 2.0) and subsequent hydroxide precipitation of Cr(III) by increasing the pH to approximately 9.0-10.0 using lime. Existing overviews of chromium removal only cover selected technologies that have traditionally been used in chromium removal. Far less attention has been paid to adsorption. Herein, we provide the first review article that provides readers an overview of the sorption capacities of commercial developed carbons and other low cost sorbents for chromium remediation. After an overview of chromium contamination is provided, more than 300 papers on chromium remediation using adsorption are discussed to provide recent information about the most widely used adsorbents applied for chromium remediation. Efforts to establish the adsorption mechanisms of Cr(III) and Cr(VI) on various adsorbents are reviewed. Chromium's impact environmental quality, sources of chromium pollution and toxicological/health effects is also briefly introduced. Interpretations of the surface interactions are offered. Particular attention is paid to comparing the sorption efficiency and capacities of commercially available activated carbons to other low cost alternatives, including an extensive table.

Adsorption↗

Ascorbate is a pro-oxidant in chromium-treated human lung cells.

The human A549 lung cell line is used in this study as a model to evaluate chromium toxicity and mutagenesis since inhalation exposure of this metal gives rise to an epidemiology that indicates the lung as a target organ of chromium toxicity. Hexavalent chromium is considered the carcinogenic form of chromium, however it must be reductively activated following uptake into cells in order to react with intracellular constituents. We have previously established that the fluorescent dyes, dichlorofluorescein (DCF) and dihydrorhodamine, are effective indicators of the reductive activation of chromium and are sensitive measures of the formation of highly reactive chromium species (RCS) intracellularly. In order to examine the role of the two common intracellular reductants, glutathione and ascorbic acid (Vitamin C) in generating RCS intracellularly, we manipulated their intracellular levels through the use of buthionine sulfoximine (BSO) or by the addition of ascorbate into the culture media. We found that the high levels of glutathione in this cancer cell line lowered endogenous oxidation levels markedly, and that, by decreasing intracellular glutathione, BSO not only generated a higher background level of endogenous intracellular oxidation but the chromium-stimulated oxidation also increased markedly. Contrary to it appellation as an anti-oxidant, ascorbic acid stimulated a strong pro-oxidant response upon chromium treatment and this pro-oxidant response was evident regardless of the levels of glutathione in the cells. Based on these results, we conclude that ascorbic acid acts as a pro-oxidant in chromium-treated cells.

Antioxidants↗

Excess chromium alters uptake and translocation of certain nutrients in citrullus.

Citrullus plants were grown in refined sand with varying levels of chromium to determine their tolerance limit to excess chromium. The plants were maintained in control nutrient solution for 24 days and on the 25th day chromium as dichromate was added at 0.05, 0.1, 0.2, 0.3 and 0.4 mM. A control set of plants was grown in the same nutrient solution without chromium. At chromium levels >0.2 mM plants showed growth depression, with chlorosis and loss of turgor of middle leaves. Affected leaves had narrow lamina; tendrils were thin, short and did not have coiling property. Later chlorosis became severe and changed to necrosis in patches. Petiole along with lamina became wilted, rugged and hung down due to complete loss of water. At lower chromium concentration, (0.05, 0.1 and 0.2 mM) only depression in growth was observed. With increase in chromium concentration of nutrient solution accumulation of chromium in different parts of Citrullus was increased. Increase in concentrations of phosphorus, manganese and decrease in iron, copper, zinc and sulphur were observed in leaves. Toxicity of chromium was greater at 0.2-0.4 mM, compared to lower concentrations. Threshold of toxicity and toxicity of Cr in old leaves were, respectively, 0.9 and 3.9 microg g(-1) dry matter of citrullus.

Chromium↗

Effects of chromium extract on cytokine release by mononuclear cells.

We have evaluated the effects of chromium extract on the release by peripheral blood mononuclear cells (PBMCs) of cytokines favouring bone resorption. Furthermore, we have evaluated whether the chromium effects could be correlated with the activation and proliferation of PBMCs. Cell cultures were maintained in serum-free medium (AIM-V), in order to avoid the interference of exogenous growth factors. Increasing concentrations of chromium extract, ranging between 3 and 100%, were added to culture medium. Cytokine release (IL-1beta, TNFalpha, IL-6, GM-CSF and IFNgamma) was assessed on both PBMCs cultured with AIM-V only (unstimulated PBMC) and PBMCs cultured with AIM-V plus phytohaemagglutinina (PHA-stimulated PBMC). The activation and proliferation of PBMCs were evaluated by assessing DNA synthesis and soluble IL-2 receptor release, in order to determine whether an IL-2-dependent immune response can be induced by chromium. Our results show that in unstimulated PBMCs chromium ions slightly increased the release of pro-inflammatory cytokines, such as TNFalpha and IL-6, even though the increase is not significant. On the contrary, the different concentrations of chromium extract significantly inhibited the response to PHA stimulation, as shown by the decrease in IL-6 and sIL-2r release, and by the influence on cell viability and DNA synthesis. Both these effects are undesirable and support hypotheses on the biological effects of chromium. The continuous release of chromium from the implant could induce in PBMCs the release of bone-resorbing cytokines, which in the long term could be responsible for irreversible tissue damage. Moreover, chromium seems to inhibit the IL-2-dependent response of PBMCs, so that they are not able to trigger an efficient cell-mediated immune response.

Bone Resorption↗

Kinetics of removal of chromium from water and electronic process wastewater by ion exchange resins: 1200H, 1500H and IRN97H.

The removal of chromium from aqueous solution by an ion exchange resin is described. Ion exchange resins 1200H, 1500H and IRN97H show a remarkable increase in sorption capacity for chromium, compared to other adsorbents. The adsorption process, which is pH dependent show maximum removal of chromium in the pH range 2-6 for an initial chromium concentration of 10mg/l. The metal ion adsorption obeyed linear, Langmuir and Freundlich isotherms. The adsorption of chromium on these cation exchange resins follows first-order reversible kinetics and pseudo-first-order kinetics. The intraparticle diffusion of chromium on ion exchange resins represents the rate-limiting step. The uptake of chromium by the ion exchange resins was reversible and thus have good potential for the removal/recovery of chromium from aqueous solutions. We conclude that such ion exchange resins can be used for the efficient removal of chromium from water and wastewater.

Adsorption↗

Natural occurrence of hexavalent chromium in the Aromas Red Sands Aquifer, California.

To address increasing concerns of chromium contamination in the drinking water of Santa Cruz County, we designed a study to investigate the source(s) and spatial gradients of the chromium concentration and speciation in local aquifers. This study was catalyzed by a report (January 2001) bythe Soquel Creek Water District of elevated hexavalent chromium concentrations ranging from 6 to 36 microg L(-1), approaching the state's maximum concentration limit of 50 microg L(-1), in the Aromas Red Sands aquifer. To test the accuracy of those preliminary measurements, we collected groundwater using trace metal clean techniques from 11 sites in Santa Cruz County, including 10 from the aquifer with reportedly elevated chromium concentrations and 1 from an adjacent aquifer, the Purisima, and analyzed them fortotal chromium using inductively couple plasma mass spectrometry. Nine of the reportedly 10 contaminated sites had total chromium concentrations ranging from 5 to 39 microg L(-1), while one from the control site was below the limit of detection (0.01 microg L(-1)). We also measured the speciation of chromium at all sites using a solid supported membrane extraction coupled with graphite furnace atomic absorption spectrometry and determined that on average 84% of total chromium was Cr(VI). In addition to the groundwater analyses, a series of extractions were performed on sediment samples from both the Aromas Red Sands and Purisima aquifers. These tests were used to empirically characterize sediment trace metal (Cr, Fe, Mn) distributions in five phases providing information about the origin, availability, reactivity, and mobilization of these trace metals. Results from groundwater and sediment samples indicate that the chromium is naturally occurring in the Aromas Red Sands aquifer, possibly by Cr(III) mineral deposits being oxidized to Cr(VI) by manganese oxides in the aquifer.

California↗

Investigation of the threshold for allergic reactivity to chromium.

Allergy to chromium is relatively common, often in association with exposure to cement or in leather manufacture. However, in certain locations, there appears to be a relatively large cohort of chromium-sensitive individuals whose allergy cannot be explained by these common sources. In particular, this group include Israeli housewives with persistent hand eczema and concomitant patch test positivity to chromium. The causation of their allergy has been linked with relatively high levels of chromium contamination in household products. To provide further information in respect of the definition of safe levels for such products, we examined 17 chromium-allergic individuals to determine their threshold for reaction under closed patch test and repeated open application test (ROAT) conditions. The data derived indicated that, on normal skin, the patch test threshold was 10 ppm chromium; in the presence of an irritant (sodium lauryl sulfate) the threshold was closer to 1 ppm, 2/17 subjects giving 1+ reactions at this concentration. In the more realistic exposure conditions of the ROAT, 8/14 individuals failed to react to 50 ppm, whilst 3/15 reacted to 5 ppm. Interestingly, there was very poor correlation between patch test sensitivity and ROAT sensitivity. To ensure the large majority of chromium-allergic individuals do not suffer elicitation of their allergy, as well as to limit the development of new chromium-sensitive subjects, it is recommended that household products adhere to a previously published standard of a maximum limit of 5 ppm, with an ultimate target of 1 ppm contamination by chromium.

Adult↗

Dietary chromium tripicolinate supplementation reduces glucose concentrations and improves glucose tolerance in normal-weight cats.

The effect of dietary chromium supplementation on glucose and insulin metabolism in healthy, non-obese cats was evaluated. Thirty-two cats were randomly divided into four groups and fed experimental diets consisting of a standard diet with 0 ppb (control), 150 ppb, 300 ppb, or 600 ppb added chromium as chromium tripicolinate. Intravenous glucose tolerance, insulin tolerance and insulin sensitivity tests with minimal model analysis were performed before and after 6 weeks of feeding the test diets. During the glucose tolerance test, glucose concentrations, area under the glucose concentration-time curve, and glucose half-life (300 ppb only), were significantly lower after the trial in cats supplemented with 300 ppb and 600 ppb chromium, compared with values before the trial. Fasting glucose concentrations measured on a different day in the biochemistry profile were also significantly lower after supplementation with 600 ppb chromium. There were no significant differences in insulin concentrations or indices in either the glucose or insulin tolerance tests following chromium supplementation, nor were there any differences between groups before or after the dietary trial.Importantly, this study has shown a small but significant, dose-dependent improvement in glucose tolerance in healthy, non-obese cats supplemented with dietary chromium. Further long-term studies are warranted to determine if the addition of chromium to feline diets is advantageous. Cats most likely to benefit are those with glucose intolerance and insulin resistance from lack of exercise, obesity and old age. Healthy cats at risk of glucose intolerance and diabetes from underlying low insulin sensitivity or genetic factors may also benefit from long-term chromium supplementation.

Animals↗

Effects of chromium nicotinate on performance, carcase characteristics and blood chemistry of growing turkeys.

1. The objective of this trial was to study the effects of chromium nicotinate (Cr) supplementation on the performance, carcase characteristics and blood constituents of 9 to 22 week-old male turkeys. 2. Fifty-four 8-week-old male turkeys weighing 2.9 +/- 0.28 kg were allocated at random into 9 groups with 3 dietary treatments and 3 replicates. The dietary treatment was different dietary concentrations of chromium in the basal diet, to provide 0 (control), 1 or 3 mg/kg. The feeding trial lasted for 14 weeks. 3. Results showed that 1 mg/kg chromium supplementation significantly improved weight gain and food intake at 9 to 18 weeks of age but did not significantly influence performance at 19 to 22 week of age. The breast and thigh muscle were significantly increased in birds receiving 1 mg/kg chromium supplementation but were decreased by 3 mg/kg of supplementation. 4. Dietary chromium supplementation did not significantly influence other serum constituents, including insulin, HDL, VLDL+LDL, HDL-C, VLDL-C+LDL-C, total protein, albumin, and gamma-globulin at 18 and 22 weeks of age. 5. The serum triacylglycerol (TG) and uric acid contents were significantly increased, while glycerol and alpha-globulin were significantly reduced by 3 mg/kg chromium supplementation. However, 1 mg/kg chromium supplementation significantly reduced serum cholesterol and glycerol at 18-weeks old. At 22 weeks of age, 1 mg/kg chromium supplementation significantly increased serum glucose and decreased the uric acid concentration whereas 3 mg/kg chromium supplementation significantly increased the creatinine concentration and decreased beta-globulin concentration.

Animal Feed↗