[Show abstract][Hide abstract] ABSTRACT: Inhalative exposure to vanadium pentoxide (V(2)O(5)) causes lung cancer in rodents.
The aim of the study was to investigate the impact of V(2)O(5) on DNA stability in workers from a V(2)O(5) factory.
We determined DNA strand breaks in leukocytes of 52 workers and controls using the alkaline comet assay. We also investigated different parameters of chromosomal instability in lymphocytes of 23 workers and 24 controls using the cytokinesis-block micronucleus (MN) cytome method.
Seven of eight biomarkers were increased in blood cells of the workers, and vanadium plasma concentrations in plasma were 7-fold higher than in the controls (0.31 microg/L). We observed no difference in DNA migration under standard conditions, but we found increased tail lengths due to formation of oxidized purines (7%) and pyrimidines (30%) with lesion-specific enzymes (formamidopyrimidine glycosylase and endonuclease III) in the workers. Bleomycin-induced DNA migration was higher in the exposed group (25%), whereas the repair of bleomycin-induced lesions was reduced. Workers had a 2.5-fold higher MN frequency, and nucleoplasmic bridges (NPBs) and nuclear buds (Nbuds) were increased 7-fold and 3-fold, respectively. Also, apoptosis and necrosis rates were higher, but only the latter parameter reached statistical significance.
V(2)O(5) causes oxidation of DNA bases, affects DNA repair, and induces formation of MNs, NPBs, and Nbuds in blood cells, suggesting that the workers are at increased risk for cancer and other diseases that are related to DNA instability.
Environmental Health Perspectives 01/2009; 116(12):1689-93. DOI:10.1289/ehp.11438 · 7.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Immunoadsorption using protein A columns is increasingly used for selective extracorporeal removal of circulating antibodies and autoantibodies. Current apheresis systems employ reusable columns requiring long-term storage (20–50 treatment sessions). To prevent microbial growth during storage, columns are primed with ethyl mercury thiosalicylic acid (thiomerosal, .01% solution) for storage and rinsed with phosphate buffer before use. Aims: To test the hypothesis of a substantial mercury exposure in protein A immunoadsorption and to investigate the effect of adding N-acetylcysteine to the rinsing solution. Patients and Methods: Whole blood mercury levels were measured by atomic absorption spectroscopy (hydride method) before and after protein A immunoadsorption (11 patients, 26 treatments), anti-IgG-immunoadsorption (8 patients, 13 treatments) and LDL apheresis (DALI and Therasorb systems; 9 patients, 14 treatments). Results: Protein A immune apheresis treatment significantly increased blood mercury levels from a median of 5.4 µg/L (range, 1.4–37.6, normal, P This preliminary report suggests that mercury toxicity may develop in patients on regular protein A immune apheresis treatment. Given impaired renal function in many patients, any effort should be undertaken to reduce systemic mercury exposure, either by adding chelators to the rinsing solution or ideally by replacement of thiomerosal. Adding N-acetlycysteine significantly reduced mercury exposure, so that we now routinely rinse protein A columns with N-acetylcysteine before use.
Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 10/2005; 9(5). DOI:10.1111/j.1744-9987.2005.00324_5.x · 1.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Immunoadsorption is increasingly used to treat antibody-mediated autoimmune diseases. To prevent microbial growth during storage, reusable protein A-Sepharose gel columns are primed with ethyl mercury thiosalicylate (thiomersal, 0.1% solution) and rinsed with phosphate buffer before use. In this study, we tested the hypothesis of systemic mercury exposure in protein A immunoadsorption.
Whole blood mercury levels were measured by atomic absorption spectroscopy before and after protein A immunoadsorption (11 patients, 26 treatments), anti-IgG immunoadsorption (eight patients, 13 treatments) and LDL apheresis (DALI and Therasorb systems; nine patients, 14 treatments).
Patients treated with protein A immunoadsorption had significantly elevated baseline mercury levels compared with the other groups, which were not different from healthy controls. Following protein A immunoadsorption, mercury levels increased from 5.9+/-1.4 microg/l (mean+/-SEM, normal, <5 microg/l) to 32.3+/-5.7 microg/l, P<0.001). In one intensively treated patient, acute neurological toxicity developed at a mercury level of 107 microg/l. Symptoms abated slowly and did not recur after switching to a thiomersal-free system and chelation therapy. No mercury release to patients occurred in anti-IgG immunoadsorption or LDL apheresis treatments.
This preliminary report suggests that protein A immunoadsorption columns primed with thiomersal during storage may cause a sustained increase of systemic mercury concentrations, which exceed current safety recommendations in a proportion of patients. Considering the potential for mercury-induced toxicity, every effort should be undertaken to reduce systemic mercury exposure, either by adding chelators to the rinsing solution or ideally by replacement of thiomersal.
[Show abstract][Hide abstract] ABSTRACT: Mercury poisoning presents a variety of clinical pictures depending on chemical structure, the route of exposure, amount absorbed and individual factors. Thus, an injection of metallic mercury can be considered relatively harmless in contrast to inhalation of mercury vapor. Injection of elemental mercury is rare, and a total of only 78 cases have been reported in the literature over the period 1923-2000.
We report a suicide attempt by intravenous injection of approximately 8 g metallic mercury. By X-ray examination widespread multiple mercury shadows were visible in the whole lung and also in the subcutaneous region of the cubital fossa, the small pelvis and the right hypogastrium. Mercury excretion after treatment with 2,3-dimercaptopropane-1-sulfonate (DMPS) was significantly higher than in occupationally exposed workers.
The patient showed symptoms typical of acute mercury intoxication, including gastroenteritis, ulceromembranous colitis and stomatitis mercuralis. No biochemical abnormalities in hepatic or renal function occurred, despite the persistence of metallic densities in the body. The patient's lung function was normal. The patient transitionally developed erethismus and tremor mercuralis. After 1 month of DMPS treatment, the mercury levels in blood were still high and the tremor was persistent. Three years after the suicide attempt the surgical removal of residual mercury in the left fossa cubitalis was performed. The extirpation of residual mercury was successful in cutting the mercury levels to almost half. After the operation the patient showed no symptoms of chronic mercury intoxication.
Since only 1 mg of mercury per day could be removed with DMPS treatment, it can be calculated, that it would take about 8,000 daily treatments to remove a total of 8 g solely by DMPS. Although DMPS itself does not dissolve the metallic deposits, it may considerably reduce the blood level of mercury and may therefore mitigate clinical symptoms, albeit transitorily. We therefore recommend that in cases of symptomatic metallic mercury injections, where the mercury cannot be removed by surgery, the patient's condition should be managed by repeated long-term DMPS treatment in order to control blood mercury levels.
International Archives of Occupational and Environmental Health 11/2002; 75(8):581-6. DOI:10.1007/s00420-002-0363-z · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Since it is still controversial whether-low-to moderate long-term lead exposure below current threshold values causes neurobehavioural deficits in adults, we investigated executive functions of the prefrontal cortex, attention, and visuospatial and visuomotor functioning in lead-exposed subjects.
Forty-seven lead-exposed subjects with a mean blood lead (PbB) level of 30.8 microg/100 ml and 53 non-lead-exposed aged-matched subjects (PbB: 4.32 microg/100 ml) with the same socio-economic background were investigated. Both groups were also matched on verbal intelligence. Neuropsychological tests were done by the modified Wisconsin card sorting test, block design test, visual recognition test, simple reaction time, choice reaction and digit symbol substitution. Lead exposure was assessed by current and cumulative measures.
While there were significant differences in the results of the Wisconsin, block design and visual recognition tests, no differences were found in simple reaction time, choice reaction and digit symbol substitution. Significant correlations existed between current exposure and cognitive deficits. No correlation was found between cumulative exposure measures and cognitive parameters.
Our results show that PbB below 70 microg/100 ml reduce neurobehavioural abilities, particularly visuospatial abilities and executive functions referring to the prefrontal cortex. As neurobiological substrate of the prefrontal dysfunction, glutamatergic system disturbances are discussed.
International Archives of Occupational and Environmental Health 09/2002; 75(6):394-8. DOI:10.1007/s00420-002-0329-1 · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study possible genotoxic effects of occupational exposure to vanadium pentoxide, we determined DNA strand breaks (with alkaline comet assay), 8-hydroxy-2'deoxyguanosine (8-OHdG) and the frequency of sister chromatid exchange (SCE) in whole blood leukocytes or lymphocytes of 49 male workers employed in a vanadium factory in comparison to 12 non-exposed controls. In addition, vanadate has been tested in vitro to induce DNA strand breaks in whole blood cells, isolated lymphocytes and cultured human fibroblasts of healthy donors at concentrations comparable to the observed levels of vanadium in vivo. To investigate the impact of vanadate on the repair of damaged DNA, co-exposure to UV or bleomycin was used in fibroblasts, and DNA migration in the alkaline and neutral comet assay was determined. Although, exposed workers showed a significant vanadium uptake (serum: median 5.38microg/l, range 2.18-46.35microg/l) no increase in cytogenetic effects or oxidative DNA damage in leukocytes could be demonstrated. This was consistent with the observation that in vitro exposure of whole blood leukocytes and lymphocytes to vanadate caused no significant changes in DNA strand breaks below concentrations of 1microM (50microg/l). In contrast, vanadate clearly induced DNA fragmentation in cultured fibroblasts at relevant concentrations. Combined exposure of fibroblasts to vanadate/UV or vanadate/bleomycin resulted in non-repairable DNA double strand breaks (DSBs) as seen in the neutral comet assay. We conclude that exposure of human fibroblasts to vanadate effectively causes DNA strand breaks, and co-exposure of cells to other genotoxic agents may result in persistent DNA damage.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 09/2002; 519(1-2):25-35. DOI:10.1016/S1383-5718(02)00138-9 · 3.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ion release from metal implants has been suspected to increase the risk of genotoxic effects in patients wearing orthopedic metal devices. In this study we used urinary 8-hydroxydeoxyguanosine (8-OHdG) as marker of oxidative DNA damage and the frequency of sister chromatid exchanges in lymphocytes to test a possible relationship between the concentrations of chromium or cobalt and the induction of cytogenetic modifications in 46 patients with total hip replacements. A broad range of individual levels of metals has been observed in these patients: chromium in blood, 1.59-14.11 microg/L; chromium in urine, 0.79-93.80 microg/24 h; cobalt in blood, 0.77-37.80 microg/L; cobalt in urine, 2.59-166.94 microg/24 h. By linear regression analysis, no significant correlation between urinary 8OHdG or sister chromatid exchange (SCE) and the concentrations of metals was found. However, cobalt in blood as well as 8-OHdG in urine were higher in patients with implants 3-4 yr old as compared to patients with implants 1-2 yr old. Smoking significantly increased the frequency of SCE. Our data do not indicate a dependence of 8-OHdG in urine or SCE on the levels of chromium or cobalt in patients with total hip replacements.
Journal of Toxicology and Environmental Health Part A 06/2002; 65(9):655-64. DOI:10.1080/15287390252900359 · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It was our aim to study whether chronic exposure to vanadium reduces cognitive abilities. We investigated effects on attention, visuospatial and visuomotor functioning, reaction time, short-term memory, and prefrontal functioning. Forty-nine vanadium exposed subjects with a mean vanadium level in urine (VanU) of 14.4 micro/L and 49 controls (VanU: 0.8 microg/L) with the same socioeconomic background were investigated. Neuropsychological tests were done using a modified Wisconsin Card Sorting Test (WCST), Block Design Test (BDT), Visual Recognition Test (VRT), Simple Reaction Time (SRT), Choice Reaction (CR), Digit Symbol Substitution (DSS), and Digit Span (DS). Exposure was assessed by using the vanadium level in urine and serum. While there were significant differences in BDT and DSS, no differences were found in WCST, SRT, CR, and DS. Significant correlations existed between the vanadium levels in urine and serum and the cognitive deficits. Vanadium concentrations around 14.2 microg/L in urine reduce neurobehavioral abilities, particularly visuospatial abilities and attention.
Journal of Toxicology and Environmental Health Part A 06/2002; 65(9):677-83. DOI:10.1080/15287390252900377 · 2.35 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine radical-induced DNA damage and its elimination in workers exposed to quartz and in patients with silicosis, and to assess the relationship of these effects to lung function.
Blood and spontaneous urine samples were obtained from active, quartz-exposed workers without silicosis (n = 63), and from retired workers with silicosis (n = 42). Levels of 8-hydroxydeoxyguanosine (8-OHdG) were determined in peripheral blood leukocyte DNA and urine, by the use of high-performance liquid chromatography coupled with ultra violet- (UV) and electrochemical detection.
No significant differences in the mean levels of 8-OHdG in leukocyte DNA and of urinary excretion of 8-OHdG were found between silicosis patients and quartz-exposed healthy workers. However, in the group of silicosis patients with increased oxidative DNA damage the urinary excretion of 8-OHdG was lower than in the corresponding group of active workers without silicosis. In the case of silicosis, urinary 8-OHdG correlated positively, and 8-OHdG in DNA correlated negatively, with forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). Healthy workers with a personally estimated high dust exposure in the workplace showed higher levels of 8-OHdG in DNA than did workers with moderate dust exposure. No association of 8-OHdG formation and/or elimination with duration of employment, field of activity, smoking or age was found.
Our findings suggest that a less effective repair of 8-OHdG is associated with a higher degree of pulmonary airway obstruction in patients with silicosis.
International Archives of Occupational and Environmental Health 08/2000; 73(5):305-10. DOI:10.1007/s004200000117 · 2.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To determine metal concentrations in blood and urine of patients who received cobalt-chromium-alloy metal on metal hip implants.
Cobalt and chromium were determined in blood and urine of 76 patients and 26 controls by electrothermal atomic absorption spectroscopy.
A significant postoperative elevation of the metal concentrations was observed for total hip replacement patients in contrast to the control group. Twenty-nine patients exceeded the EKA (Expositionäquivalente für Krebserzeugende Arbeitsstoffe) threshold limits for cobalt in blood and for cobalt and chromium in urine. We obtained a significant correlation between cobalt in blood and cobalt in urine (r = 0.79; p < 0.005), chromium in blood and chromium in urine (r = 0.79; p < 0.005), cobalt in blood and chromium in blood (r = 0.69; p = 0.008), and cobalt in urine and chromium in urine (r = 0.95; p = 0.004).
Our findings suggest that in total hip replacements using metal-metal pairings, metal ions of the alloys are released. This release may lead to significantly elevated metal concentrations in biological fluids. Long-term studies are needed to determine the risk of metal-metal implants as a potential cause of cobalt and chromium toxicity.
Journal of toxicology. Clinical toxicology 02/1999; 37(7):839-44. DOI:10.1081/CLT-100102463