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XRCC1 protects against particulate chromate-induced chromosome damage and cytotoxicity in Chinese hamster ovary cells.

Water-insoluble hexavalent chromium compounds are well-established human lung carcinogens. Lead chromate, a model insoluble Cr(VI) compound, induces DNA damage, chromosome aberrations, and dose-dependent cell death in human and Chinese hamster ovary (CHO) cells. The relationship between lead chromate-induced DNA damage and chromosome aberrations is unknown. Our study focus was on examining the role of XRCC1 in lead chromate-induced cytotoxicity and structural chromosomal aberrations in CHO cells. Three different cell lines were used: AA8 (parental), EM9 (XRCC1 mutant), and H9T3 (EM9 complemented with human XRCC1 gene). Cytotoxicity was significantly higher in EM9 cells when compared to AA8 and H9T3 cells, indicating that XRCC1 is important for protecting cells from lead chromate particles-induced cell death. The frequency of damaged metaphase cells was not affected by XRCC1 deficiency. However, the total amount of Cr(VI)-induced chromosome damage was exacerbated by XRCC1 deficiency, and the spectrum of damage changed dramatically. Chromatid and isochromatid lesions were the most prominent aberrations induced in all cell lines. XRCC1 was essential to reduce the formation of chromatid lesions but not for isochromatid lesions. In addition, XRCC1 deficiency resulted in a dramatic increase in the number of chromatid exchanges, indicating that XRCC1 is involved in protection from lead chromate-induced chromosome instability.

Animals↗

Causes of chromate dermatitis in Poland.

A series of 250 consecutive patients with dermatitis and positive patch tests to chromate was divided into three groups: nonoccupational dermatitis (94), occupational dermatitis caused by chromate (132) and occupational dermatitis caused by allergens other than chromate (24). Only 17.2% of patients did not report harmful effects from chromium-tanned leather. Shoes were most often not tolerated. The role of matches in the development of chromate dermatitis is discussed. Observations on ash, household detergents, textiles, wood, tattooing, cement, galvanizing solutions, printer's ink, welding fumes, corrosion inhibitors and oils are described as causes of chromate dermatitis in Poland, as well as the localization of dermatitis and relevance of patch test reactions.

Adolescent↗

Reactive oxygen species produced from chromate pigments and ascorbate.

The reactions of various chromate pigments and ascorbate were investigated by an ESR spin trapping technique. Production of Cr(V) was detected directly and productions of very electrophilic reactive oxygen species (ROS) was detected via the oxidation of formate. We demonstrated previously that both dissolved oxygen and Cr (V) were essential in the production of ROS in this system, and that ROS production was inhibited by catalase. We studied here the effect of solubility of different chromate pigments: sodium, calcium, strontium, basic zinc, basic lead supported on silica, and lead and barium chromates on the production of ROS in buffered medium and cell culture medium (Dublecco's Modified Eagle medium + fetal calf serum). Sodium, calcium, basic zinc, and basic lead chromates were active in the production of ROS in presence of cell culture medium, whereas lead and barium chromates were inactive.

Ascorbic Acid↗

Comparison of the cytotoxicity, cellular uptake, and DNA-protein crosslinks induced by potassium chromate in lymphoblast cell lines derived from three different individuals.

We are trying to understand individual differences in susceptibility to chromate toxicity by comparing three different lymphoblastic cell lines derived from three different individuals. We have compared the uptake of CrO4(2-), the release of LDH from cells, the proliferation ability of the cells, and the DNA-protein crosslinks in these lymphoblastic cell lines exposed to chromate. We report here that one lymphoblastic cell line, GM0922B, appears to be considerably less sensitive than the other two cells lines to the cytotoxic effects of hexavalent chromium. The diminished sensitivity is almost twofold and can be accounted for by the decreased uptake of hexavalent chromium, which results in less lactate dehydrogenase release, and greater tolerance to chromate inhibition of cell proliferation and less DNA-protein crosslinking. This lower uptake of chromate combined with interindividual differences in extracellular Cr(VI) reducing capacity are probably the two most important determinants of genetic susceptibility to chromate toxicity.

Adult↗

Inverse relationship between renal and urinary kallikrein during chromate-induced acute renal failure in rat: urinary kallikrein excretion as a possible recovery index.

Acute renal failure (ARF) was induced in rat following a single injection of sodium chromate. A transient polyuria and a 10-fold decrease in glomerular filtration rate was immediately observed after sodium chromate administration. Urinary sodium and potassium excretion were reduced within 24 h and remained decreased for 8 to 10 days. Progressive recovery of normal renal functions, mainly electrolyte excretion and filtration rate was observed 12 days after sodium chromate administration. Urinary kallikrein excretion (UKE) was decreased only 48 h after sodium chromate administration. However the proportion of the active and inactive form excreted was unchanged. UKE remained also at a reduced level for 8 to 10 days and returned progressively to base-line level. The kallikrein content in the tissue was significantly increased immediately after sodium chromate administration and recovered normal values 12 days later. The increase of kallikrein in the tissue is more likely unspecific due to impaired protein transport than a specific stimulation of renal kallikrein biosynthesis. The decreased UKE may indicate a distal tubular reversible dysfunction in this ARF model. These reductions in electrolyte excretion, glomerular filtration and UKE were associated with selective morphological lesions. Whereas the glomeruli were intact, important damages affected proximal tubule cells which appeared necrotic and showed presence of vacuoles, liquefaction of cytoplasmic material and lost of microvilli. Less marked lesions were however observed in distal tubules, particularly large vacuoles were present at the apical poles of the tubule cells, the sites of kallikrein secretion. These distal damages may be involved in the increase of tissue concentration and in the decrease of UKE.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Uptake of chromate by rat thymocytes and role of glutathione in its cytoplasmic reduction.

1. Chromate is taken up by rat thymocytes over a wide range of extracellular chromate concentrations (0.074 +/- 5.0 mM). 2. Chromate uptake followed Michaelis-Menten kinetics and was inhibited by 4-acetamido-4'-isothiocyano-stilbene-2,2'-disulphonic acid, suggesting that the anion carrier was responsible for the uptake by rat thymocytes. 3. The decrease in chromate uptake by the thiol(SH)-blocking agent diethyl maleate, the increased chromate uptake caused by the thiol-protecting agent dithiothreitol, and the reduction of glutathione/glutathione disulphide ratio indicated that the maintenance of the integrity of SH-groups greatly influenced the uptake and reduction of Cr(VI), and that glutathione may be responsible for the intracellular reduction of Cr(VI) to Cr(III).

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

In vitro transformation of BHK21 cells grown in the presence of calcium chromate.

Concentrations of 0.25 and 0.5 mug/ml calcium chromate (CaCrO4-2H2O)dissolved in Dulbecco's medium were found to alter the growth behavior of BHK21 cells in culture. Treated cells grew as shortened fibroblasts and in random orientation. The changes detected during the first two weeks of culture in the presence of the metal became more pronounced as the number of growth passages increased. In addition to the alterations noted above, chromate-treated cells grew into large clusters in Methocel (an alternative technique to the agar suspension system), while untreated cells underwent, at most, only one or two divisions in Methocel. These alterations in growth properties were irreversible and persisted after removal of the treated cells from chromate-containing medium, suggesting that a heritable change had occurred as opposed to a transient, chromate-dependent alteration of cell growth. This experimental observation suggests that chromate salts and perhaps salts of other metals can transform BHK21 cells in vitro or can select for spontaneously transformed cells.

Animals↗

[Adsorption behavior of chromate onto activated carbon particles].

In this paper, the adsorption behavior of chromate onto activated carbon particles was studied as a function of pH, flow rate and the concentration of tested anion. The results showed that chromate anion was not only reduced but also adsorbed by activated carbon particles, the percentages of reduction and adsorption were strongly dependent on the pH value and the flow rate. In the medium of pH < 10, chromate anion could be adsorbed directly onto the activated carbon particles and the adsorbed chromate could be eluted from activated carbon particles by 1 mol/L NaOH without valence change. The reduced product of chromate anion was mainly Cr (VI), Cr(VI) could be adsorbed in the pH > 4 medium by the activated carbon particles and eluted with 1%H2SO4.

Adsorption↗

[Chromates: resistance and detoxification in bacteria].

Derivatives of hexavalent chromium (chromates and dichromates) are highly toxic and have been shown to be mutagens and carcinogens. These compounds are often disposed to the environment as a result of diverse industrial procedures. The presence of chromates selects bacterial strains possessing chromate resistance determinants, commonly carried by plasmids. Some bacteria are able to reduce hexavalent chromium to trivalent chromium which is much less toxic. Bacterial strains combining both properties, resistance to and reduction of chromate, are potentially useful for decontamination of sewage or other refuse contaminated by chromates.

Amino Acid Sequence↗

Effect of ascorbic acid on DNA damage, cytotoxicity, glutathione reductase, and formation of paramagnetic chromium in Chinese hamster V-79 cells treated with sodium chromate(VI).

The effect of pretreatment with ascorbic acid (vitamin C) on chromate-induced DNA damage, cytotoxicity, and enzyme inhibition as well as on the cellular reduction of chromium(VI) was investigated using Chinese hamster V-79 cells. Cellular pretreatment with nontoxic levels of 1 mM ascorbic acid for 24 h prior to exposure resulted in a significant increase (1.7-fold) in cellular levels of this vitamin. Alkaline elution assays demonstrated that this pretreatment decreased cellular levels of Na2CrO4-induced alkali-labile sites while the numbers of DNA-protein crosslinks produced by chromate increased. In colony-forming assays, pretreatment with ascorbic acid enhanced the cytotoxicity of chromate. However, the inhibition of glutathione reductase attributed to Na2CrO4 was attenuated by this pretreatment. Under the same experimental condition, the uptake of chromate in pretreated cells was found to increase. ESR studies revealed that cellular pretreatment with ascorbic acid reduced the level of chromium(V) intermediate and increased the level of chromium(III) complex, indicating that cellular reduction of chromium(VI) to chromium(III) was accelerated by this vitamin. These results suggest that ascorbic acid decreases chromate-induced alkali-labile sites and chromium inhibition of glutathione reductase, but it enhances DNA-protein cross-links and cytotoxicity caused by this metal through its ability to directly reduce chromium(VI).

Animals↗

Influence of vitamin B2 on formation of chromium(V), alkali-labile sites, and lethality of sodium chromate(VI) in Chinese hamster V-79 cells.

The effect of vitamin B2 on the cellular reduction and cytotoxicity of chromate(VI) was studied using Chinese hamster V-79 cells. Electron spin resonance studies showed that incubation of cells with Na2CrO4 resulted in the formation of both chromium(V) and chromium(III) complex and that cellular pretreatment with riboflavin (Vitamin B2) for 24 h prior to exposure increased the level of chromium(V) complex, but the level of chromium(III) remained unchanged. Analysis of flavin derivatives revealed that pretreatment with vitamin B2 increased free riboflavin without altering flavin adenine dinucleotide and flavin mononucleotide. In addition, the level of the flavoenzyme glutathione reductase, which is capable of reducing chromate, was unaffected by pretreatment with vitamin B2. However, treatment of cells with vitamin B2 and Na2CrO4 augmented the inhibition of glutathione reductase attributable to Na2CrO4 alone. Using a colony-forming assay, pretreatment with vitamin B2 resulted in a decrease of cytotoxicity after exposure to the lethal concentration of chromate (15 microM) but did not affect the cytotoxicity at sublethal concentration of this metal (5-7.5 microM). Alkaline elution studies demonstrated that Na2CrO4 induced alkali-labile sites in the DNA of cells in a concentration-dependent manner (5-15 microM) and pretreatment with vitamin B2 resulted in an increase of these DNA lesions at all concentrations of Na2CrO4. The results, showing that vitamin B2 enhances chromate-induced alkali-labile lesions and chromium inhibition of glutathione reductase, might be due to an increase of chromium(V) species, possibly through its ability to directly reduce chromium(VI). The results also suggest that the extent of DNA lesions induced by chromate may not correlate directly with the cytotoxic effects of this metal.

Animals↗

[Chromate eczema in food, domestic and cleaning occupations].

No chromium in the form of chromate was found in flour and baking powders. Contradictory reports published elsewhere have not been substantiated. The occasional incidence of chromate allergy observed in the domestic services trades, bakeries, curing houses and bottling plant were found to be due to traces of chromate in the following substances: wood ash 0.23 ppm, lignite ash 0.05 to 1.7 ppm, refractory brick 0.5 to 0.9 ppm, certain alkaline scouring agents 0.1 to 0.2 ppm, suds produced when washing chromate-containing glasses 0.13 to 1.61 ppm. Furthermore, when surface treating heated cr-ni sheet steel sheet panels of 10 square centimetre size with alkalis or organic acids (acetic acid) it was possible to dissolve 0.33 to 60.0 micrograms of chromium as chromate.

Chromates↗

High hydrostatic pressure potentiation of the toxic effects of chromate in cell culture.

Development of hyperbaric welding has created the need for new occupational health standards. We have used cell cultures to investigate effects of high pressure chromate on the toxicity of the welding-fume component, chromate. The results indicate that pressure caused rounding-up of cells and changes in F-actin filaments, and that these effects were related to the extent of high pressure and independent of exposure duration. When exposing the Flow 5000 cells to chromate (1-5 microM) the amount of disrupted F-actin fibers was found to depend on the concentration applied and the duration of exposure. The amount of cell-associated chromate was the same for 1 h exposure at 1 and 150 bar. The fraction of rounded cells after exposure to 1 microM chromate and 100 bar for 18 h was higher than would be expected if the effects were purely additive.

Actins↗

Multiple sclerosis: abnormalities in luminance, chromatic, and temporal function at multiple retinal sites.

Visual function was assessed in a group of patients with multiple sclerosis (MS) and in a group of matched normal controls. In these patients the disease was relatively mild. For each subject, measures of a range of psychophysical visual functions were carried out at multiple sites in each eye. Previous reports have only included some of these functions. Here, luminance threshold, two-flash resolution, perceptual latency, luminance critical flicker frequency (CFF), and chromatic CFF were all measured. Variabilities of these functions and correlation between chromatic and luminance CFFs were also evaluated. For both the MS group and the normal control group, the correlations between pairs of visual parameters were not overall significantly greater than chance level. The MS group did give a significantly reduced value relative to the normal group for luminance CFF and for the gradient of the plot of chromatic CFF against luminance CFF. This group was then subdivided according to history of visual involvement. The subgroup with previous visual symptoms had significant impairment for luminance threshold, variability of luminance threshold, luminance CFF, variability of two-flash resolution, and for the gradient of the plot of chromatic CFF against luminance CFF. The subgroup without previous visual symptoms showed no significant impairment for any individual parameter, although the gradient of the plot of chromatic CFF against luminance CFF was lower than normal.

Adult↗

Changes in the human visually evoked cortical potential in response to chromatic modulation of a sinusoidal grating.

Human visually evoked cortical potentials (VECPs) were recorded from 4 subjects in response to the counterphase alternation of an equal brightness chromatic grating pattern. The pattern was constructed from 2 monochromatic sinusoidal gratings registered 180 deg out of phase. Eleven wavelengths from 450 to 650 nm (at 20 nm intervals) were used. Each wavelength was paired in the grating stimulus with every other to produce a total of 55 different chromatic gratings. The chromatic modulation depth (contrast) of each grating was varied and resulting VECPs were recorded. VECP amplitude was found to vary linearly with log chromatic modulation depth. VECP threshold values were inferred by extrapolation of linear regression lines to zero VECP amplitude. Chromatic modulation sensitivity functions were derived and a multidimensional scaling analysis of the data for each subject was performed. The data were adequately described by a two-dimensional geometric configuration of the 11 wavelengths used. The configurations were similar in shape to those obtained psychophysically by Butler and Riggs (1978) Vision Res. 18, 1407-1416, who used a similar stimulus pattern. Their shapes are consistent with an opponent-color model of color vision.

Adult↗

Changes in perceived color due to chromatic interactions.

Studies of chromatic induction have generally examined either (a) the effects of a chromatic surround on a neutral test field, or (b) the effects of one spectral hue on another. To investigate how colors interact in other regions of color space an experiment was designed using fifteen test stimuli scattered through C.I.E. color space. The perceived hue of each stimulus was matched on its own and in the presence of five inducing stimuli. Matching was done both with and without a lens to correct axial chromatic aberration, which was found to be a significant prereceptoral factor influencing perceived colour. With chromatic aberration corrected the overall pattern of chromatic changes can be explained neither by receptor processes alone, nor by opponent channel processes alone. But a reasonable fit can be obtained if changes are allowed to take place in both levels of the system.

Color Perception↗

Positive colored afterimages from the figure-ground configurations of colored lights: effects of chromaticity, luminance and a spatial parameter of the adapting stimuli.

Colored afterimages were obtained after the eye was exposed to the adapting field consisting of the figure-ground configuration of colored lights with the same hue and different saturation. When a colored patch was surrounded by a more saturated field, the color of the afterimage was similar to that of the previous patch (positive afterimage). By measuring the threshold chromaticity difference between the patch and the surround for the production of the positive afterimage, the effects of the chromaticity, luminance and a spatial parameter of the adapting field were determined. The obtained threshold chromaticity differences increased with an increase in the saturation of the adapting field, and with a decrease in the surround luminance. When the adapting field consisted of an equiluminous saturation-modulated rectangular grating, the threshold chromaticity difference curves showed similar properties as those of the contrast thresholds for equiluminous chromaticity-modulated gratings. The results suggest the existence of a set of mechanisms at higher-order level in the visual system, tuning the difference in hue and/or saturation across contours.

Adaptation, Ocular↗

Binocular measurements of chromatic adaptation.

In this paper we present asymmetric matching data that were obtained with a binocular presentation method. Our main motivation was the question whether chromatic adaptation, one of the important mechanisms that contribute to colour constancy, has evolved towards a better performance in the range of colours that are present in the natural image. For the eye adapted to a bluish illuminant for example the presence of an object with a deep yellow colour is very unlikely. So, it was expected that the colour difference between adapting light and target has an influence on the extent of chromatic adaptation. It was found that the colour shift in the observers' matches that can be attributed to chromatic adaptation indeed has a maximum. The location of the maximum, however, was unexpected, i.e. colour differences between target and adapting light that lie around 0.05 u'v'-chromaticity units. Additionally, several models for chromatic adaptation were fitted to our data. It was found that, except for the simple von Kries model, Retinex Theory and difference contrast, a number of models gave good predictions for the L-wave and M-wave fundamental systems, but that predictions for the S-wave system were less accurate.

Adaptation, Ocular↗