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Effects of NADH and H(2)O(2) on chromate-induced human erythrocytes hemoglobin oxidation and peroxidation.

The effects of NADH and H(2)O(2) on chromate-induced human erythrocyte hemoglobin oxidation and peroxidation were studied. It was observed that NADH decreases the levels of chromate-induced human erythrocyte hemoglobin oxidation and peroxidation. H(2)O(2) decreases the levels of chromate-induced hemoglobin oxidation, but increases the levels of chromate-induced peroxidation. The ability of H(2)O(2) to decrease the levels of chromate-induced hemoglobin oxidation is higher than that observed for NADH. Furthermore, H(2)O(2) increases the inhibitory effect of NADH on chromate-induced hemoglobin oxidation, but decreases the NADH effect on chromate-induced peroxidation. The meaning of these results is discussed in terms of involvement of reactive chromium(V) species and reactive oxygen species in the mechanism by which chromate induces its effects in human erythrocytes.

Cell Culture Techniques↗

CA-125 levels after surgical exploration and radioactive chromic phosphate in ovarian cancer patients.

Trends in CA-125 levels after completion of therapy in ovarian cancer patients who received intraperitoneal radioactive chromic phosphate therapy (32P) after primary surgical resection or second-look surgery were evaluated. Ninety patients who underwent surgical exploration and 32P were reviewed. Twenty-nine patients were excluded due to insufficient number of CA-125 levels or recurrence within 12 months, with 61 patients with serial CA-125 levels and no evidence of disease for 12 months available for analysis. 32P followed initial resection in 24 patients (16 Stage I, 3 Stage II, 5 Stage III). 32P followed chemotherapy and second-look procedures in 37 patients (4 Stage I, 3 Stage II, 27 Stage III, 3 Stage IV). Elevated CA-125 levels were present in 25 (41%) patients within 12 months of 32P (46% after primary exploration, 38% after second-look). The degree of CA-125 elevation (U/ml) was 30-100 (23%), 100-200 (11%), and >200 (7%). Of the 25 patients with an elevated CA-125, the elevation persisted more than 4 months in 11 (44%). All but two patients had normal CA-125 levels by 12 months. An abnormal elevation in CA-125 was seen in 33% of patients 4 months after receiving 32P and abdominal surgery, with values ranging as high as 500 U/ml. Although elevations in CA-125 are reported following surgery alone, the duration of elevation appears to be longer with 32P. Therefore, persistent elevations of CA-125 following 32P between 4 and 12 months should be judged with caution as they may not reflect recurrent disease.

CA-125 Antigen↗

Solvent and temperature dependence of spin echo dephasing for chromium(V) and vanadyl complexes in glassy solution.

The solvent and temperature dependence of the rate constant for spin echo dephasing, 1/Tm, for 0.2 to 1.2 mM glassy solutions of chromyl bis(1-hydroxy-cyclohexanecarboxylic acid), CrO(HCA)-2; aquo vanadyl ion, VO2+ (aq), and vanadyl bis(trifluoroacetylacetonate), VO(tfac)2 were examined. At low temperatures where 1/T1 << 1/Tm, 1/Tm in 1:1 H2O:glycerol is dominated by solvent protons. At low temperature 1/Tm increases in the order 1:1 H2O:glycerol or 9:1 CF3CH2OH:ethyleneglycol (no methyl groups) < 9:1 i-PrOH:MeOH (hindered methyl groups) < 9:1 n-PrOH:MeOH (less hindered methyl groups). This solvent dependence of 1/Tm is similar to that observed for nitroxyl radicals, which indicates that the effect of solvent methyl groups on spin-echo dephasing at low temperature is quite general. At higher temperatures the echo dephasing is dominated by spin-lattice relaxation and is concentration dependent. As the glass softens, echo dephasing is dominated by the onset of molecular tumbling.

Chromium↗

Hexavalent chromium-contaminated soils: options for risk assessment and risk management.

Risk assessment involves establishing scientifically defensible dose-response relationships for end points of concern. For Cr(VI)-contaminated soils, this includes conducting dose-response assessments for blood, liver, and kidney toxicity following oral exposure; lung cancer following inhalation exposure; and allergic contact dermatitis following dermal exposure. This dose-response information is then integrated with a site-specific exposure assessment (or default assumptions) in order to develop a site-specific (or generic) soil criterion within the framework of a comprehensive risk characterization. Risk managers develop cleanup standards designed to protect against all possible adverse effects, taking into account these site-specific (or generic) criteria and other factors such as technical feasibility, cost-benefit analyses, and socio-political concerns. Recently a push for cost-benefit analyses of environmental decisions has occurred, further supporting the need for risk assessors to prepare a comprehensive risk characterization, with its attendant uncertainties. These risk assessment and management issues are brought to the forefront by risk assessors and risk managers dealing with Cr(VI)-contaminated soils. This article offers a review and analysis of the risk characterization of Cr(VI)-contaminated soils, showing that the differing toxicities with route of exposures do not necessarily lead to different characterizations or risk. Soil concentrations in the range of 130 to 450 ppm appear to protect against noncancer toxicity from oral exposure, cancer toxicity from inhalation exposure, and allergic contact dermatitis from dermal exposure.

Administration, Inhalation↗

Establishing an occupational exposure limit for hexavalent chromium in the European Union.

A Criteria Document for hexavalent chromium [Cr(VI)], currently under preparation at the Institute of Occupational Health, University of Birmingham, is intended for use in setting an occupational exposure limit (OEL) for Cr(VI) in the European Union (EU). The requirement for establishing OELs, specifically known as indicative limit values, in the EU is set out in Council Directive 80/1107/EEC, amended by Council Directive 88/642/EEC. To facilitate this procedure the Commission has set up a Scientific Committee for Occupational Exposure Limits to Chemical Agents. The Committee, which is composed of independent scientific experts from member states, is responsible for reviewing available scientific data. A Criteria Document forms the basis of the scientific data considered during this process and contains an up-to-date, critical evaluation of available information which is relevant to setting an exposure limit. After consideration of the scientific data for a particular substance, the Committee advises the Commission on setting a health-based OEL. Consideration of other questions such as technical matters and socioeconomic issues occurs during later stages of the procedure, before an OEL is finally adopted. The procedure allows for consultation with interested parties. The Criteria Document for Cr(VI) contains sections on substance identification, chemical and physical properties, production and use data, recent data on occupational exposure, current methods for measurement and analysis, and toxicology. The toxicology section contains a critical evaluation of both human and animal data and forms a major part of the document. This section enables identification of critical health effects associated with exposure to Cr(VI) and consideration of dose-response relationships and provides the basis for any risk assessment and recommendation for an OEL.

Carcinogens↗

Environmental monitoring of chromium in air, soil, and water.

Historical uses of chromium have resulted in its widespread release into the environment. In recent years, a significant amount of research has evaluated the impact of chromium on human health and the environment. Additionally, numerous analytical methods have been developed to identify and quantitate chromium in environmental media in response to various state and federal mandates such as CERCLA, RCRA, CWA, CAA, and SWDA. Due to the significant toxicity differences between trivalent [Cr(III)] and hexavalent [Cr(VI)] chromium, it is essential that chromium be quantified in these two distinct valence states to assess the potential risks to exposure to each in environmental media. Speciation is equally important because of their marked differences in environmental behavior. As the knowledge of risks associated with each valence state has grown and regulatory requirements have evolved, methods to accurately quantitate these species at ever-decreasing concentrations within environmental media have also evolved. This paper addresses the challenges of chromium species quantitation and some of the most relevant current methods used for environmental monitoring, including ASTM Method D5281 for air, SW-846 Methods 3060A, 7196A and 7199 for soils, sediments, and waste, and U.S. EPA Method 218.6 for water.

Air Pollutants↗

Analytical methodology for biological monitoring of chromium.

Analytical aspects associated with biological and ambient monitoring are outlined with an emphasis on processing samples at very low concentrations and optimization of analytical methods. Verification of chromium determination in body fluids by means of "Round Robin" tests is discussed. In addition, an approach for indirect valency discrimination of chromium species relevant in biological monitoring is presented. Application of voltammetry for model tests is described. This is aimed at studying the reaction of hexavalent chromium in human plasma. As a result, a natural reducing capacity of plasma of up to 2 ppm chromium(VI) was detected and quantified as an individual biological index. Furthermore, the effect of ascorbic acid on the reduction of chromium(VI) in plasma is demonstrated and quantitative bases for therapy in cases of accidental intoxication are discussed.

Animals↗

Absorption and elimination of trivalent and hexavalent chromium in humans following ingestion of a bolus dose in drinking water.

These studies investigate the magnitude and valence state of chromium absorbed following plausible drinking water exposures to chromium(VI). Four adult male volunteers ingested a single dose of 5 mg Cr (in 0.5 liters deionized water) in three choromium mixtures: (1) Cr(III) chloride (CrCl3), (2) potassium dichromate reduced with orange juice (cr(III)-OJ); and (3) potassium dichromate [Cr(VI)]. Blood and urine chromium levels were followed for 1-3 days prior to and up to 12 days after ingestion. The three mixtures showed quite different pharmacokinetic patterns. CrCl3 was poorly absorbed (estimated 0.13% bioavailability) and rapidly eliminated in urine (excretion half-life, approximately 10 hr), whereas Cr(III)-OJ was absorbed more efficiently (0.60% bioavailability) but more slowly (half-life, approximately 17 hr), and Cr(VI) had the highest bioavailability (6.9%) and the longest half-life (approximately 39 hr). All three chromium mixtures caused temporary elevations in red blood cell (RBC) and plasma chromium concentrations, but the magnitude and duration of elevation showed a clear trend (Cr(VI) > Cr(III)-OJ > CrCl3). The data suggest that nearly all the ingested Cr(VI) was reduced to Cr(III) before entering the bloodstream based on comparison to RBC and plasma chromium patterns in animals exposed to high doses of Cr(VI). These findings support our prior work which suggests that water-soluble organic complexes of Cr(III) formed during the reduction of Cr(VI) in vivo explain the patterns of blood uptake and urinary excretion in humans at drinking water concentrations of 10 mg/liter or less.

Administration, Oral↗

Cytotoxicity, apoptosis, and in vitro DNA damage induced by potassium chromate.

Cr(6+) is a known human cytotoxic and carcinogenic agent that requires intracellular reduction for activation. We have analyzed the cytotoxic and DNA binding properties of K(2)CrO(4) (Cr(6+)) in comparison with those of Cl(3)Cr (Cr(3+)). The results indicate that K(2)CrO(4) exhibits higher cytotoxicity than Cl(3)Cr in several human and murine cell lines. The cytotoxic activity of K(2)CrO(4) is also indicated by the fact that is able to produce cell killing through apoptosis in cisplatin-resistant cells transformed by H-ras oncogene. Moreover, in vitro DNA binding experiments show that, in the presence of ascorbate (the major intracellular reductant of Cr(6+)), K(2)CrO(4) induces both interstrand cross-links and strand breaks. Because the chromate anion is by itself unreactive toward DNA, these data suggest that the cytotoxicity of K(2)CrO(4) may be associated with the DNA binding of reactive intermediate chromium species resulting from reduction of Cr(6+).

Animals↗

Hard metal-induced disease: effects of metal cations in vitro on guinea pig isolated airways.

Inhalation of dust from hard metal (HM), a mixture of tungsten carbide, cobalt, and other metals, can cause interstitial alveolitis, fibrosis, and asthma in the workplace. Some effects of HM could occur after the metals dissolve in the lung. We examined whether chloride salts of metals in HM alloys can elicit responses or modify reactivity to methacholine (MCh) or responses to electric field stimulation (EFS) in guinea pig tracheal strips. In unstimulated strips, Co(2+), Cd(2+), and Ni(2+) evoked contractions (>3 x 10(-6) M), while Ta(5+), Zn(2+), Cr(2+), and Cr(3+) caused weak relaxations (>10(-5) M). In strips contracted with MCh (3 x 10(-7) M), Co(2+) and Ni(2+) also caused relaxation in lower concentrations while the other metals caused weak relaxation only in high concentrations (>10(-4) M). The metals were generally without effect on reactivity to MCh, except that Cd(2+) inhibited and Ni(2+) potentiated some responses. The effects of selected metals (10(-6) M; Cr(3+), Ni(2+), Cd(2+), and Co(2+)) on EFS-induced contractile and relaxant responses were examined (+/-MCh; +/-10(-6) M indomethacin (Indo), 30 min). No metal had any effect on the excitatory nonadrenergic, noncholinergic-mediated contraction phase. Cd(2+) and Ni(2+) inhibited cholinergically mediated contractions of unstimulated strips (+Indo), whereas Cr(3+) both inhibited (-MCh, -Indo) and potentiated (-Indo,+MCh; +Indo, +MCh) contractile responses. Cr(3+) was the only metal to inhibit the inhibitory nonadrenergic, noncholinergic-mediated relaxation phase (+/-MCh; -Indo). Co(2+) had no effect at all. The results suggest that smooth muscle tone and nerves in the airways could be targets of cationic metals after they dissolve in the lung.

Alloys↗

The measurement of radiation doses from P32 chromic phosphate therapy of the peritoneum using SPECT.

Single photon emission computed tomography (SPECT) has been shown to be of value in estimating the radiation dose to the peritoneum from 32P therapy. Simple dosimetry calculations, assuming uniform irradiation of tissue, indicate that radiation doses of approximately 40 Gy to the peritoneal surface are achieved. However, the images show that the radionuclide distribution is non-uniform, giving rise to radiation dose variations of at least a factor of 10.

Chromium↗

Reflection contrast microscopy within chrome-alum haematoxylin stained thick tissue-sections.

This paper introduces two innovations in reflection contrast microscopy (RCM): (1) an extended application for qualitative light microscopic investigations; and (2) a novel method for quantification in cytochemistry. (1) We found out that RCM cannot only be used for surface characterizations and in thin sections but also within thick tissue-sections. The use of the RCM technique is demonstrated on slides of the supraoptic nucleus (SON) of the rat stained with chrome-alum haematoxylin: Among all the stained structures only neurosecretory granules are found to cause reflections. The visualization of the neurosecretion and its distribution is more distinct and of sharper contrast than in bright field microscopy. (2) The improved differentiation allows the quantification of neurosecretion in tissue-sections by combining RCM with grey-scale image analysis.

Animals↗

Urinary excretion of chromium as an indicator of exposure to trivalent chromium sulphate in leather tanning.

Two workers exposed to trivalent chromium sulphate in a leather tannery had high concentrations of chromium in the urine. The concentration of chromium showed a workshift-related diurnal fluctuation, but it was remarkably high even after a vacation, indicating accumulation of chromium in the body. The concentrations of chromium in the workplace air, as collected on filters using standard techniques, were below 30 micrograms/m3. The chromium in the air was present in the form of large droplets not collected by the standard techniques. In the blood stream, chromium was transported exclusively in the plasma. No absorption of chromium through the skin could be detected. Absorption from the gastrointestinal tract was calculated to explain the findings.

Adult↗

Cytochemical evaluation of sperm and lymphocyte DNA content after treatment with 5 N HCl.

In situ as well as extra situm cytochemical methods were used to investigate why the observed Feulgen-DNA value of sperm versus lymphocyte cells is lower than expected. After treatment with 5 N HCl, in situ experiments involving the GCA reaction and the UV cytophotometry showed the loss of DNA in sperm nuclei to be 12% more than that in lymphocyte nuclei. Extra situm study of sperm and lymphocytes treated with 5 N HCl showed the phosphate and DABA contents of sperm to be 35% and 23%, respectively, less than those of lymphocytes. The data suggest that sperm chromatin is much more sensitive than somatic chromatin to HCl depolymerization during the Feulgen reaction, and this can tentatively be attributed to the protein complement of sperm chromatin.

Animals↗

The involvement of nucleosomes in Giemsa staining of chromosomes. A new hypothesis on the banding mechanism.

A new hypothesis is proposed on the involvement of nucleosomes in Giemsa banding of chromosomes. Giemsa staining as well as the concomitant swelling can be explained as an insertion of the triple charged hydrophobic dye complex between the negatively-charged super-coiled helical DNA and the denatured histone cores of the nucleosomes still present in the fixed chromosomes. New cytochemical data and recent results from biochemical literature on nucleosomes are presented in support of this hypothesis. Chromosomes are stained by the Giemsa procedure in a purple (magenta) colour. Giemsa staining of DNA and histone (isolated or in a simple mixture) in model experiments results in different colours, indicating that a higher order configuration of these chromosomal components lies at the basis of the Giemsa method. Cytophotometry of Giemsa dye absorbance of chromosomes shows that the banding in the case of saline pretreatment is due to a relative absence of the complex in the faintly coloured bands (interbands). Pretreatment with trypsin results in an increase in Giemsa dye uptake in the stained bands. Cytophotometric measurements of free phosphate groups before and after pretreatment with saline, reveal a blocking of about half of the free phosphate groups indicating that a substantial number of free amino groups is still present in the fixed chromosomes. Glutaraldehyde treatment inhibited Giemsa-banding irreversibly while the formaldehyde-induced disappearance of the bands could be restored by a washing procedure. These results correlate with those of biochemical nucleosome studies using the same aldehydes. Based on these findings and on the known properties of nucleosomes, a mechanism is proposed that explains the collapse of the chromosome structure when fixed chromosomes are transferred to aqueous buffer solutions. During homogeneous Giemsa staining reswelling of the unpretreated chromosome is explained by insertion of the hydrophobic Giemsa complex between the hydrophobic nucleosome cores and the superhelix DNA. Selective Giemsa staining of the AT-enriched bands after saline pretreatment is thought to be due to the, biochemically well-documented, higher affinity of arginine-rich proteins present in the core histones for GC-enriched DNA, which prevents the insertion of the Giemsa complex in the interbands. Production of Giemsa bands by trypsin pretreatment can be related to the action of this enzyme on the H1 histones and subsequent charge rearrangements.(ABSTRACT TRUNCATED AT 400 WORDS)

Azure Stains↗