Increased Lipogenesis Is Important for Hexavalent Chromium-Transformed Lung Cells and Xenograft Tumor Growth.

Hexavalent chromium, Cr(VI), is a known carcinogen and environmental health concern. It has been established that reactive oxygen species, genomic instability, and DNA damage repair deficiency are important contributors to the Cr(VI)-induced carcinogenesis mechanism. However, some hallmarks of cancer remain under-researched regarding the mechanism behind Cr(VI)-induced carcinogenesis. Increased lipogenesis is important to carcinogenesis and tumorigenesis in multiple types of cancers, yet the role increased lipogenesis has in Cr(VI) carcinogenesis is unclear. We report here that Cr(VI)-induced transformation of three human lung cell lines (BEAS-2B, BEP2D, and WTHBF-6) resulted in increased lipogenesis (palmitic acid levels), and Cr(VI)-transformed cells had an increased expression of key lipogenesis proteins (ATP citrate lyase [ACLY], acetyl-CoA carboxylase [ACC1], and fatty acid synthase [FASN]). We also determined that the Cr(VI)-transformed cells did not exhibit an increase in fatty acid oxidation or lipid droplets compared to their passage-matched control cells. Additionally, we observed increases in ACLY, ACC1, and FASN in lung tumor tissue compared with normal-adjacent lung tissue (in chromate workers that died of chromate-induced tumors). Next, using a known FASN inhibitor (C75), we treated Cr(VI)-transformed BEAS-2B with this inhibitor and measured cell growth, FASN protein expression, and growth in soft agar. We observed that FASN inhibition results in a decreased protein expression, decreased cell growth, and the inhibition of colony growth in soft agar. Next, using shRNA to knock down the FASN protein in Cr(VI)-transformed BEAS-2B cells, we saw a decrease in FASN protein expression and a loss of the xenograft tumor development of Cr(VI)-transformed BEAS-2B cells. These results demonstrate that FASN is important for Cr(VI)-transformed cell growth and cancer properties. In conclusion, these data show that Cr(VI)-transformation in vitro caused an increase in lipogenesis, and that this increase is vital for Cr(VI)-transformed cells.

Chromate exposure induces DNA hypermethylation of the mismatch repair gene MLH1 in lung cancer.

Hexavalent chromium is recognized as a human carcinogen. Our previous studies revealed that lung cancer (LC) in chromate-exposed workers (chromate LC) had molecular features of frequent microsatellite instability (MSI), repression of MLH1 level, and aberrant DNA methylation of several tumor-suppressor genes, including MLH1. In the present study, we quantitatively investigated MLH1-promoter methylation status using bisulfite pyrosequencing of paired tumorous/nontumorous tissues from chromate and nonchromate LCs to determine the effect of chromate exposure on MLH1-promoter methylation. The methylation level of MLH1 promoter was significantly higher in chromate LC tumors (P < .001) than nonchromate LC tumors and, among chromate LC, significantly higher in tumorous tissue than nontumorous tissue (P = .004). Moreover, the methylation level of MLH1 promoter in normal lung tissue tended to be higher in chromate LC than nonchromate LC (P = .062). In addition, LC with reduced levels of MLH1 showed significantly higher methylation levels of MLH1 promoter than LC exhibiting normal MLH1 levels (P = .019). Moreover, immunohistochemical analyses determined that levels of SUV39H1, an H3K9me2-related methyltransferase, were higher in chromate LC than nonchromate LC (P = .076). Furthermore, we evaluated three DNA double-strand break-repair genes (MRE11, RAD50, and DNA-PKcs) as possible targets of MSI by fragment-length polymorphism analysis, revealing the mutation frequency of RAD50 as significantly higher in chromate LC than nonchromate LC (P = .047). These results suggest that chromate exposure might induce MLH1 hypermethylation in LC as a mechanism of chromate-induced carcinogenesis.

Can reducing cosmetic substances help prevent chromate contact allergy?

BACKGROUND: Allergic contact dermatitis caused by Cr(VI) is often severe and difficult to treat. Therefore, primary prevention is a main goal but, secondary prevention can be valuable to ease the symptoms or prevent relapse of Cr(VI) dermatitis when sensitization has occurred. Barrier creams have been tried for many chemical substances, but until now there is no successful barrier cream against Cr(VI). OBJECTIVES: To investigate the ability of reducing agents to transform Cr(VI) into Cr(III) in an experimental situation, in order to find suitable chemicals to investigate for possible use in a barrier cream. METHODS: The capacity to reduce the amount of Cr(VI) was analyzed in water solutions of acetylcysteine, cysteine, dihydroxyacetone, glutathione, and iron sulfate heptahydrate. Thereafter the reducing capacity of acetylcysteine, dihydroxyacetone, glutathione, and iron sulfate on the amount of Cr(VI) in cement extracts was investigated. The content of Cr(VI) in the test solutions and in the cement extracts was estimated by the diphenyl carbazide spot test. RESULTS: All of the chosen chemicals reduced the amount of Cr(VI) in the test solutions and in the cement extracts to some extent. The reducing capacity was most prominent for iron sulfate. CONCLUSION: A reducing capacity was found for all chosen chemicals.

Treatment of Cells and Tissues with Chromate Maximizes Mitochondrial 2Fe2S EPR Signals.

In a previous study on chromate toxicity, an increase in the 2Fe2S electron paramagnetic resonance (EPR) signal from mitochondria was found upon addition of chromate to human bronchial epithelial cells and bovine airway tissue ex vivo. This study was undertaken to show that a chromate-induced increase in the 2Fe2S EPR signal is a general phenomenon that can be used as a low-temperature EPR method to determine the maximum concentration of 2Fe2S centers in mitochondria. First, the low-temperature EPR method to determine the concentration of 2Fe2S clusters in cells and tissues is fully developed for other cells and tissues. The EPR signal for the 2Fe2S clusters N1b in Complex I and/or S1 in Complex II and the 2Fe2S cluster in xanthine oxidoreductase in rat liver tissue do not change in intensity because these clusters are already reduced; however, the EPR signals for N2, the terminal cluster in Complex I, and N4, the cluster preceding the terminal cluster, decrease upon adding chromate. More surprising to us, the EPR signals for N3, the cluster preceding the 2Fe2S cluster in Complex I, also decrease upon adding chromate. Moreover, this method is used to obtain the concentration of the 2Fe2S clusters in white blood cells where the 2Fe2S signal is mostly oxidized before treatment with chromate and becomes reduced and EPR detectable after treatment with chromate. The increase of the g = 1.94 2Fe2S EPR signal upon the addition of chromate can thus be used to obtain the relative steady-state concentration of the 2Fe2S clusters and steady-state concentration of Complex I and/or Complex II in mitochondria.

Coronary stent restenosis and the association with allergy to metal content of 316L stainless steel.

BACKGROUND: Most intra-coronary stents in use are made of 316 L stainless steel, which contains nickel, chromate and molybdenum. Whether inflammatory and allergic reactions to metals contribute to in-stent restenosis is still a matter of debate. AIM: The aim of this study was to ascertain the relationship between metal allergy and the occurrence of in-stent restenosis. METHODS: Ninety-nine adult patients who underwent two cardiac catheterisations, up to two years apart, were included in the study. Seventy patients had patent stents at the second angiogram (patent stent group) and 29 were found to have in-stent restenosis (restenosis group). All patients underwent patch testing with the relevant metals and the 316L stainless steel plate. RESULTS: Twenty-eight (28.3%) patients were found to have an allergy to at least one metal. There was no significant difference in the prevalence of metal allergy between the patent stent group and the restenosis group (28.6 and 27.6%, respectively; p = 0.921). CONCLUSIONS: Our data do not support the theory that contact allergy plays a role in the pathogenesis of in-stent restenosis.

Differential expression of the PAL gene family in rice seedlings exposed to chromium by microarray analysis.

Phenylalanine ammonia-lyase (PAL) is one of the principle enzymes involved in plant's secondary metabolism. Expression of individual isogene from the PAL gene family is variable with species of plants in responses to different stresses. In this study, transcriptome analysis of the PAL gene family in rice seedlings exposed to potassium chromate Cr(VI) or chromium nitrate Cr(III) was conducted using Agilent 44K rice microarray and real-time quantitative RT-PCR. Uptake and accumulation of both Cr species by rice seedlings and their effect on PAL activity were also determined. Three days of Cr exposure led to significant accumulation of Cr in plant tissues, but majority being in roots rather than shoots. Changes of PAL activities in rice tissues were evident from both Cr treatments. Individual isogene from the rice PAL gene family was expressed differentially in response to both Cr variants. Comparing gene expression between two Cr treatments, only osPAL2 and osPAL4 genes were expressed in similar patterns. Also, gene expression pattern was inconsistent in both plant tissues. Results indicated that expression of individual isoform from the rice PAL gene family is tissue, and stimulus specific under different Cr exposure, suggesting their different detoxification strategies for decreasing or eliminating Cr stresses.

[Effects on human peripheral erythrocytes of long-term occupational contact with chromate].

Objective: To investigate the effects on human peripheral blood erythrocytes of long-term occupational contact with chromate. Methods: A dynamic cohort study was conducted of chromate-exposed workers (343 cases) and non-chromate-exposed workers (73 cases) at a chromate production enterprise who were selected according to specific inclusion and exclusion criteria from 2010 to 2015. Personal information and chromate exposure information were obtained by questionnaire. A generalized estimating equation was employed to analyze the effects on human peripheral blood erythrocytes of long-term occupational contact with chromate, controlling for age, gender, smoking, alcohol consumption and body mass index. Results: The mean ages and working ages of those entering the cohort study were 36.67 ±6.78 and 38.47 ± 7.18, respectively, for the exposure group and 8.39 ± 6.02 and 12.86 ± 8.34, respectively, for the control group. The erythrocyte content [(4.73±0.46), (4.81±0.53), (4.41±0.45)]×1012/L in the peripheral blood in the chromate exposure group was lower than that [(4.76±0.42), (4.95±0.45), (4.47±0.39)]×1012/L in the control group for the years 2010, 2011, 2012 and 2014 (t values were 0.38, 1.96, 0.92 and 1.21; P values were 0.703, 0.051, 0.358 and 0.227, respectively). The correlations between the years 2010 and 2011, 2011 and 2012, 2012 and 2014, and 2014 and 2015 were 0.667, 0.464,-0.070 and 0.020, respectively (P<0.001). The RR for males and those that consumed alcohol were 0.661 (95% CI: 0.616-0.709) and 0.910 (95% CI: 0.811- 1.201), respectively. Compared with the control group, the risk of reduced erythrocyte levels in the peripheral blood was increased by 0.915 (95% CI: 0.852- 0.982) in the chromate-exposed group. Conclusions: The erythrocyte content of peripheral blood was reduced after long-term exposure to chromate. Maleness and alcohol consumption were factors that increased the risk of reduced peripheral blood erythrocytes in the chromate-exposed population.

Cement-Induced Chromate Occupational Allergic Contact Dermatitis.

BACKGROUND: Hexavalent chromium in cement is a common cause of occupational allergic contact dermatitis (OACD). METHODS: Analysis of patch test data during 1999 to 2013 was done. Patients with cement-induced chromate OACD filled the Dermatology Life Quality Index, graded 1 to 5. RESULTS: Of 4846 consecutive patients who were patch tested, 146 (3%) were chromate-sensitive. Of 46 (31.5%) who presented with chromate OACD, 27 (59%) had cement-induced chromate OACD. The proportion of chromate-sensitive patients with clinically relevant cement exposure increased from 7.7% in 2002 to 2004 to 28.7% in 2011 to 2013 (P = 0.04). The median age of presentation was younger than for other chromate-sensitive patients (32 vs 42 years). Hand eczema (88.9%) was the most frequent clinical presentation. Of the 27 with cement-induced chromate OACD, 21 (77.8%) had ongoing dermatitis at the time of the review. Although 14/27 (51.9%) changed their occupation to avoid exposure to cement, symptoms persisted in 9/14 (64.3%). Prolonged exposure to cement before development of symptoms was associated with chronicity. All the symptomatic patients experienced at least a moderate effect on their quality of life (grade 3 or higher on the Dermatology Life Quality Index). CONCLUSIONS: We recommend the adoption of the European legislation in Israel, to reduce the prevalence of chromate OACD from cement.

Chromate Allergy in Northern Israel in Relation to Exposure to Cement and Detergents.

BACKGROUND: The prevalence of chromate allergy has declined worldwide in the last decades. OBJECTIVES: The aim of the study was to assess tendencies in chromate allergy in northern Israel and its possible causes. METHODS: Retrospective analysis of patch test data during 1999-2013 and a review of the medical records of patients with chromate allergy were conducted. RESULTS: A total of 4846 consecutive patients were patch tested, of whom 146 (3%) were found to be chromate sensitive. The prevalence of chromate allergy decreased significantly from 4.7% in 1999-2001 to 2.8% in 2002-2004 (P = 0.02). Since then, no significant fluctuations have occurred. A gradual and consistent decline in chromate allergy was recorded among women from 4.8% in 1999-2001 to 2.3% in 2008-2010. Cement (18.4%) was the most frequent source of exposure and was mainly observed in men. The frequency of clinically relevant cement exposure increased significantly from 7.7% in 2002-2004 to 28.7% in 2011-2013 (P = 0.04), whereas the frequency of relevant detergent exposure decreased significantly from 25% in 1999-2001 to 5.7% in 2011-2013 (P = 0.04). Hand (68.5%) was the most frequently involved anatomical site. CONCLUSIONS: The prevalence of chromate allergy in northern Israel is stable in the general population and gradually decreasing among women. These changes may be caused by reduced exposure to water-soluble hexavalent chromium in detergents but not in cement.

Characterization and structure prediction of partial length protein sequences of pcoA, pcoR and chrB genes from heavy metal resistant bacteria from the Klip River, South Africa.

The Klip River has suffered from severe anthropogenic effects from industrial activities such as mining. Long-term exposure to heavy metal pollution has led to the development of heavy metal resistant strains of Pseudomonas sp. KR23, Lysinibacillus sp. KR25, and E. coli KR29. The objectives of this study were to characterize the genetics of copper and chromate resistance of the isolates. Copper and chromate resistance determinants were cloned and sequenced. Open reading frames (ORFs) related to the genes CopA and CopR were identified in E. coli KR29, PcoA in Lysinibacillus sp. KR25 and none related to chromate resistance were detected. The 3D-models predicted by I-TASSER disclose that the PcoA proteins consist of ß-sheets, which form a part of the cupredoxin domain of the CopA copper resistance family of genes. The model for PcoR_29 revealed the presence of a helix turn helix; this forms part of a DNA binding protein, which is part of a heavy metal transcriptional regulator. The bacterial strains were cured using ethidium bromide. The genes encoding for heavy metal resistance and antibiotic resistance were found to be located on the chromosome for both Pseudomonas sp. (KR23) and E. coli (KR29). For Lysinibacillus (KR25) the heavy metal resistance determinants are suspected to be located on a mobile genetic element, which was not detected using gel electrophoresis.

Assessing the suitability of 8-OHdG and micronuclei as genotoxic biomarkers in chromate-exposed workers: a cross-sectional study.

OBJECTIVES: We aimed to investigate suitable conditions of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and micronucleus (MN) as genotoxic biomarkers at different levels of occupational chromate exposure. DESIGN: A cross-sectional study was used. PARTICIPANTS: 84 workers who were exposed to chromate for at least 1 year were chosen as the chromate exposed group, while 30 non-exposed individuals were used as controls. MAIN OUTCOME MEASURES: Environmental and biological exposure to chromate was respectively assessed by measuring the concentration of chromate in the air (CrA) and blood (CrB) by inductively coupled plasma mass spectrometer (ICP-MS) in all participants. MN indicators, including micronucleus cell count (MNCC), micro-nucleus count (MNC), nuclear bridge (NPB) and nuclear bud (NBUD) were calculated by the cytokinesis-block micronucleus test (CBMN), while the urinary 8-OHdG was measured by the ELISA method and normalised by the concentration of Cre. RESULTS: Compared with the control group, the levels of CrA, CrB, MNCC, MNC and 8-OHdG in the chromate-exposed group were all significantly higher (p<0.05). There were positive correlations between log(8-OHdG) and LnMNCC or LnMNC (r=0.377 and 0.362). The levels of LnMNCC, LnMNC and log (8-OHdG) all have parabola correlations with the concentration of CrB. However, there was a significantly positive correlation between log (8-OHdG) and CrB when the CrB level was below 10.50 µg/L (r=0.355), while a positive correlation was also found between LnMNCC or LnMNC and CrB when the CrB level was lower than 9.10 µg/L (r=0.365 and 0.269, respectively). CONCLUSIONS: MN and 8-OHdG can be used as genotoxic biomarkers in the chromate-exposed group, but it is only when CrB levels are lower than 9.10 and 10.50 µg/L, respectively, that they can accurately reflect the degree of genetic damage.

Plasma exchange successfully treats central pontine myelinolysis after acute hypernatremia from intravenous sodium bicarbonate therapy.

BACKGROUND: Osmotic demyelination syndrome (ODS) primarily occurs after rapid correction of severe hyponatremia. There are no proven effective therapies for ODS, but we describe the first case showing the successful treatment of central pontine myelinolysis (CPM) by plasma exchange, which occurred after rapid development of hypernatremia from intravenous sodium bicarbonate therapy. CASE PRESENTATION: A 40-year-old woman presented with general weakness, hypokalemia, and metabolic acidosis. The patient was treated with oral and intravenous potassium chloride, along with intravenous sodium bicarbonate. Although her bicarbonate deficit was 365 mEq, we treated her with an overdose of intravenous sodium bicarbonate, 480 mEq for 24 hours, due to the severity of her acidemia and her altered mental status. The next day, she developed hypernatremia with serum sodium levels rising from 142.8 mEq/L to 172.8 mEq/L. Six days after developing hypernatremia, she exhibited tetraparesis, drooling, difficulty swallowing, and dysarthria, and a brain MRI revealed high signal intensity in the central pons with sparing of the peripheral portion, suggesting CPM. We diagnosed her with CPM associated with the rapid development of hypernatremia after intravenous sodium bicarbonate therapy and treated her with plasma exchange. After two consecutive plasma exchange sessions, her neurologic symptoms were markedly improved except for mild diplopia. After the plasma exchange sessions, we examined the patient to determine the reason for her symptoms upon presentation to the hospital. She had normal anion gap metabolic acidosis, low blood bicarbonate levels, a urine pH of 6.5, and a calyceal stone in her left kidney. We performed a sodium bicarbonate loading test and diagnosed distal renal tubular acidosis (RTA). We also found that she had Sjögren's syndrome after a positive screen for anti-Lo, anti-Ra, and after the results of Schirmer's test and a lower lip biopsy. She was discharged and treated as an outpatient with oral sodium bicarbonate and potassium chloride. CONCLUSION: This case indicates that serum sodium concentrations should be carefully monitored in patients with distal RTA receiving intravenous sodium bicarbonate therapy. We should keep in mind that acute hypernatremia and CPM can be associated with intravenous sodium bicarbonate therapy, and that CPM due to acute hypernatremia may be effectively treated with plasma exchange.

A pilot risk assessment study of strontium chromate among painters in the aeronautical industry.

OBJECTIVE: A method for risk assessment of occupational exposure to strontium chromate (SrCrO4) in painters employed in the aeronautical industry is described. METHODS: Assessment was made of 21 male workers of the painting division, potentially exposed to SrCrO4 (exposed), and 20 male workers of the tests and warehouse divisions (controls). All participants completed a questionnaire about work tasks, lifestyle habits, hobbies and diet. Personal active sampling for the determination of Cr and Sr was performed both during paint-spraying and during other operations in the painting division area. On the same day as environmental sampling, urine samples were collected at the beginning and end of the work shift in exposed workers to determine urinary chromium (CrU), and only at the end of the shift in controls. In the second half of the shift, a blood sample was taken in 10 exposed workers and 10 controls, to determine Cr in plasma (CrP) and in red blood cells (CrRBC). RESULTS: During paint-spraying, Cr concentrations ranged between 1.38 and 17.10 microg/m3, versus 0.02 to 0.07 microg/mi in the painting division area, while the Sr concentration was 22.90 microg/m3 in the paint-spray booth versus 0.07 microg/m3 in the painting division area. CrU at the end of the work shift, CrP and CrRBC, did not show significant differences between exposed workers and controls. Moreover, in exposed workers there were no differences between CrU measured at the beginning and at the end of the work shift. CONCLUSIONS: This approach, consisting of simultaneous environmental and biological monitoring, suggested no absorption of chromium in the painters thanks to the efficacy of the technical, organizational and personal protection measures adopted. However, the evident exposure to high levels of SrCrO4 during paint-spraying highlights how absolutely essential it is to ensure strict compliance with all the preventive measures foreseen by the EU and national regulations for occupational exposure to carcinogens.

[Effect of occupational combined exposure of chromium and iron on erythrocyte metabolism].

OBJECTIVE: To investigate the effect of combined occupational exposure of chromium and iron on erythrocyte metabolism, and the possible mechanism. METHODS: A total of 115 chromate production workers were selected in a chemical factory of Jinan as exposure group, Dec, 2008, and 60 healthy residents from a community which was far away from the factory were enrolled as control group. Environmental concentrations of chromium and iron were collected by filter membrane sampling and determined. The peripheral blood of subjects were collected for determination of chromium, iron, copper in whole blood and folate, vitamin B12 in serum, mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) and correlation analysis was conducted. RESULTS: The median (quartile interval) concentration of air-chromium and air-iron in workplace were 9.0 (10.5) and 11.2 (10.1) µg/m³, respectively, which were significantly higher than that of the control (0.1 (0.1) and 7.2 (2.5) µg/m³) (all P values < 0.01). Blood-chromium and blood-iron of the exposed group were 15.5 (14.1) µg/L and (895.1 ± 90.2) mg/L, which were significantly higher than the counterpart of the control (3.6(2.0) µg/L, (563.7 ± 49.3) mg/L) (all P values < 0.01). Serum folate ((6.9 ± 2.5) µg/L), serum vitamin B12 ((396.4 ± 177.0) µg/L) and blood copper ((777.6 ± 103.5) µg/L) of the exposed group were all significantly lower comparing to the control group ((558.0 ± 330.8), (8.1 ± 3.8), (812.1 ± 94.6) µg/L) (all P values < 0.05). The relationships between blood chromium and serum folate, serum vitamin B12 were statistical significant (r = -0.319 and -0.293, P < 0.01). Both serum vitamin B12 and blood copper correlated with mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) (r = -0.223, -0.242, -0.261, -0.292, all P values < 0.01). CONCLUSION: Combined chromium and iron exposure existed in the workplace. Adverse effect of Chromium on human erythrocyte may via folate and vitamin B12 metabolism, while iron may via copper metabolism.

[Dynamic observation of pulmonary ventilation function in workers contacting chromate].

OBJECTIVE: To explore changes of pulmonary ventilation function of chromate exposed workers. METHODS: Ninety-five chromate exposed workers were used as exposure group, and forty-two workers without chromate exposure as control group. Pulmonary ventilation function was performed two times in the winter of 2010 and 2011 respectively in one chromate manufactured factory in Henan Province. RESULTS: In 2010, pulmonary ventilation function of chromate exposed group compared with the control group, forced vital capacity [FVC, (75.38±15.23) L vs. (83.99±26.52)L], forced expiratory volume in one second [FEV1,(82.13±16.51)L vs.(91.24±30.03)L], FEV1/FVC(112.10±13.23 vs. 116.18±11.32), peak expiratory flow [PEF,(74.31±28.09) L/s vs.(78.13±28.34)L/s], maximal expiratory flow [MEF,(101.23±46.37) L/s vs. (110.02±41.40)L/s], maximum ventilation volume [MVV,(90.82± 16.89)L/min vs. (99.95±22.61)L/min]were significantly decreased(P<0.05). In 2011, pulmonary ventilation function of chromate exposed group compared with the control group, FVC[(72.34±14.18)L vs.(81.01±20.79)L], FEV1[(76.04±16.20)L vs.(86.71±24.53)L], FEV1/FVC(109.10±16.18 vs.114.08±10.79), PEF[(71.35±24.87 )L/s vs.(75.36±20.67)L/s], MEF[(96.51±30.17)L/s vs.(107.11±34.81)L/s], MVV[(84.85±21.22)L/min vs. (96.77±22.63)L/min] were also significantly decreased(P<0.05). 2011 compared with 2010, pulmonary ventilation function of chromate exposed group FEV1[(76.04±16.20)L vs.( 82.13±16.51)L], MEF[(96.51±30.17)L/s vs. (101.23±46.37)L/s], MVV[(84.85±21.22)L/min vs. (90.82±16.89)L/min] were significantly decreased(P<0.05). Comparing the classification and category of pulmonary dysfunction based on FVC, FEV1, FVC/ FEV1, no difference was found for classification between the two groups and the category of pulmonary dysfunction almost belongs to limit type, which did not change with exposed time. CONCLUSION: Chronic chromate exposure can cause significant effects on pulmonary function of the workers, and the types of work in production can affect the results.

Oxidative DNA damage and global DNA hypomethylation are related to folate deficiency in chromate manufacturing workers.

Exposure to hexavalent chromium [Cr (VI)] can cause DNA damage, genetic instability and increase the risk of cancer development. Folate deficiency affects DNA methylation and reduces the stability of the genetic material. However, the correlation between folate deficiency and DNA damage has never been clearly elucidated in chromate workers. In this study, we recruited one hundred and fifteen workers from chromate producing facilities as testing subjects and sixty local residents without chromium exposure history served as controls. The results showed an evident accumulation of Cr in peripheral red blood cells accompanied by a significantly decreased serum folate in chromate exposed workers. The decreased serum folate was associated with an increased urinary 8-hydroxy-2'-deoxyguanosine, DNA strand breaks and global DNA hypomethylation. These findings suggest that chronic occupational chromate exposure could induce folate depletion, which may further promote DNA damages and global DNA hypomethylation. Adequate folate supplement may provide benefit to chromate sufferers in stabilization of genetic material and reduce the risk of cancer development.

Caffeic acid inhibits chromium(VI)-induced oxidative stress and changes in brush border membrane enzymes in rat intestine.

We have previously shown that a single oral dose of potassium dichromate results in a decrease in the activities of several brush border membrane enzymes, produces oxidative stress, and alters the activities of several antioxidant enzymes in the small intestine of rats. In the present study, we have investigated the effect of treatment with the dietary antioxidant caffeic acid on potassium dichromate-induced biochemical changes in the rat intestine. Adult male Wistar rats were randomly divided into four groups: control, potassium dichromate alone, caffeic acid alone, and potassium dichromate + caffeic acid. Administration of a single oral dose of potassium dichromate alone (100 mg/kg body mass) led to a decrease in the activities of brush border membrane enzymes, increase in lipid peroxidation, decrease in sulfhydryl groups, and changes in the activities of several antioxidant enzymes. Two oral doses of caffeic acid (each of 250 mg/kg body mass) greatly attenuated the potassium dichromate-induced changes in all these parameters, but the administration of caffeic acid alone had no effect. Thus, caffeic acid is an effective agent in reducing the effects of potassium dichromate on the intestine and could prove to be useful in alleviating the toxicity of chromium(VI) compounds.

Effects of chronic chromate exposure on human serum prostate specific antigen: a cross sectional study.

The detrimental effect of chronic chromium (Cr) exposure on the prostate has never been studied. Here, we report the prostate specific antigen (PSA) changes in occupational chromate exposed workers. In this study, eighty six male occupational chromate exposed workers and forty five age-matched controls were recruited. The concentration of Cr in urine (U-Cr), serum total PSA (tPSA), free PSA (fPSA), high sensitive C reactive protein (Hs-CRP) and peripheral white blood cells count (WBC) were measured. The results show that the U-Cr, serum tPSA, Hs-CRP and WBC were significantly higher in Cr exposed workers when compared to the controls. Contrastively, the serum fPSA level in Cr exposed workers was lower than controls. A significant positive correlation between U-Cr and serum tPSA was observed. Multiple linear regression analysis revealed that serum tPSA and fPSA level was statistically associated with the serum Hs-CRP and U-Cr concentration in Cr exposed workers. These observations suggested that chronic Cr exposure could produce potential prostate injury and the nonspecific inflammation at least might be one of the reasons to explain the elevated concentration of tPSA in chronic occupational chromate exposed workers.