The influence of the intensity of smoking and years of work in the metallurgy on pro-oxidant/antioxidant balance in the blood of smelters.

The aim of this study was to investigate the effect of cigarette smoking and occupational exposure to heavy metals on the degree of pro-oxidant/antioxidant imbalance in smelters. The investigations were performed on the blood and urine of 400 subjects: 300 male copper smelters and 100 nonexposed male subjects. Biological material was divided into three groups: nonsmokers, those who smoked less than 20 cigarettes a day and those who smoked more than 20 cigarettes a day. The results showed a significant increase in the concentration of lead, cadmium and arsenic in the blood and urine of smelters, while smoking more than 20 cigarettes a day caused a further increase in the concentration of these metals. The level of malondialdehyde was approximately twofold higher in the plasma of the smelters compared to the control group. We have observed a disturbance in the level of antioxidants in erythrocyte lysate manifested by an increase in metallothionein and glutathione concentrations as well as superoxide dismutase and glutathione peroxidase activities and the decrease in glutathione S-transferase activity. Cigarette smoking, years of work in metallurgy and age of smelters were additional factors significantly affecting the pro-oxidant/antioxidant balance.

Relationship between occupational exposure to lead and local arterial stiffness and left ventricular diastolic function in individuals with arterial hypertension.

Relationship between occupational exposure to lead and frequency of complications in persons with arterial hypertension has been poorly investigated. This study aimed at evaluation of the relationship between occupational exposure to lead and manifestation of an increased local arterial stiffness and left ventricular diastolic dysfunction. The studies included 105 men (mean age: 44.47±9.12years) with arterial hypertension, treated with hypotensive drugs: group I - men occupationally exposed to lead (n=53), and group II - men not exposed to lead (n=52). In echocardiographic examination, the left ventricular diastolic dysfunction was diagnosed significantly more frequently in group I than in group II. In eTracking examination mean values of stiffness parameter (ß), augmentation index (AI) and one-point pulse wave velocity (PWV-ß) were significantly higher and mean values of arterial compliance (AC) were significantly lower in group I than in group II. The logistic regression showed that in the group of persons with arterial hypertension occupationally exposed to lead a more advanced age, higher blood lead concentration and higher mean values of augmentation index represent independent risk factors of left ventricular diastolic dysfunction. The multifactorial regression showed that amongst persons with arterial hypertension occupationally exposed to lead higher blood zinc protoporphyrin concentration, a more advanced age and higher value of body mass index (BMI) represent independent risk factors of an increased local arterial stiffness. In summary, we should note that in the group of persons with arterial hypertension occupationally exposed to lead the study has demonstrated a significantly more frequent manifestation of left ventricular diastolic dysfunction and an increase in local arterial stiffness.

[Relationship between chronic exposure to lead, cadmium and manganese, blood pressure values and incidence of arterial hypertension]. / Zwiazek miedzy przewleklym narazeniem na olów, kadm i mangan a wartoscia cisnienia tetniczego oraz wystepowaniem nadcisnienia tetniczego.

BACKGROUND: Chronic exposure to heavy metals may cause the increase in blood pressure (BP). The aim of the study was to determine the relationship between chronic exposure to lead, cadmium and manganese, BP values and the incidence of arterial hypertension (AT). MATERIAL AND METHODS: The study group consisted of 171 men occupationally and chronically exposed to heavy metals (group I), and 19 healthy men included into the control group (group II). Concentrations of lead and cadmium in blood, manganese in serum, free protoporphyrins in erytrocytes, and delta aminolevulinic acid in urine as well as blood pressure were measured. Six subgroups of the exposed individuals were chosen: those exposed to lead (subgroup A), to cadmium--(subgroup B), to manganese (subgroup C), to lead and cadmium (subgroup D), to lead and manganese (subgroup E), and to cadmium and manganese (subgroup F). RESULTS: In group I, the values of systolic blood pressure and mean blood pressure were statistically significantly higher than in group II. Moreover, systolic blood pressure was significantly higher in subgroups A, B, D and E in comparison with group II. Diastolic pressure was significantly lower in group II than in subgroups A and D, and mean blood pressure was significantly higher in subgroups A, D and E in comparison with group II. The incidence of arterial hypertension was significantly higher in subgroups A and D than in group II. The independent risk factors for the incidence of arterial hypertension in the study group were higher blood concentrations of lead and, cadmium. CONCLUSIONS: In men occupationally exposed to heavy metals there is a tendency to higher levels of BP. Higher blood concentrations of lead and cadmium were found to be the independent risk factors for the incidence of arterial hypertension in subjects chronically exposed to heavy metals.

[Proteomic analysis of protein profiles in some pathological stages of the human organism]. / Analiza proteomiczna profili bialkowych w niektórych stanach patologicznych ludzkiego organizmu.

Two-dimensional gel electrophoresis (2-DE) is a widely used method for separation of the proteins of a proteome and it enables their detection in a large concentration range. Sample preparation for isoelectric focusing and SDS-PAGE electrophoresis as well as spot visualization determines the quality of the obtained protein maps. Computer analysis of the proteome maps allows comparison and detection differences in protein profiles. In combination with mass spectrometry (MS) it enables the identification of a single protein. Low-abundance proteins of physiological body fluids are considered as the potential source of diagnostic biomarkers. These are obtained by such techniques as affinity chromatography, immunoaffinity, and ultrafiltration. A combination of proteomic and metabonomic analysis provides a collection of new markers which are helpful in modern medical diagnostics. The combination of the 2-DE technique and 1H MRS enables monitoring mild cognitive impairment(MCI) and the evolution of Alzheimer disease (AD). Proteome analysis of the liver and red blood cells of patients with diagnosed schizophrenia indicates the importance of analyzing external tissue, not only cerebrospinal fluid, in the diagnosis of this disease. Proteomic techniques enable the identification of new biomarkers in rheumatic disease by analyzing plasma, articular fluid and tissues. New protein biomarkers (in plasma, serum, pancreatic juice, urine) enable earlier cancer diagnosis and disease monitoring. Proteome analysis of maternal serum and amniotic fluid creates the possibility detection of protein markers in prenatal tests diagnosing Down's syndrome. Proteomic studies enable assessment of the influence of environmental contamination on the immunological system.

[Influence of tobacco smoking on amylase activity in serum persons occupational exposed to heavy metals]. / Wplyw palenia papierosów na aktywnosc amylazy w surowicy osób narazonych zawodowo na metale ciezkie.

The newest conducted investigations showed the significant role of tobacco smoking in inducing pathological changes in pancreas. Additionally exposure to heavy metals presents on polluted environment influences on function this organ. However, the mechanism of development of these changes has not been fully recognised. The aim of this study is to prove the influence of tobacco smoking on total amylase and termolabile amylase activity in serum of smoking and nonsmoking healthy persons and workers at cooper foundry in Legnica occupationally exposed to heavy metals: cadmium, arsenic, lead. Blood has been collected from 28 healthy persons and 60 founders. The enzyme total activity has been determined using the colorimetric method with substrate 1,2-odilauryl-rac-glycero-3-glutaric acid-(6-methylresorufin) ester. The thermolability activity has been determined using the thermolability test. It has been noted significant higher total amylase and thermolabile amylase activity in serum of smoking healthy persons (p < 0.0002; p < 0.002) and of non-smoking (p < 0.001; p < 0.01) and smoking founders (p < 0.0004; p < 0.001) comparison with non-smoking healthy persons. It hasn't been found significant differences in total and thermolabile amylase activity in smoking founders and non-smoking founders. The fact that there are significant differences in serum amylase activity in serum of smoking and nonsmoking founders in comparison with nonsmoking healthy persons prove a significant influence of exposure to heavy metals on exocrine function of pancreas.

[Urinary N-acetyl-beta-D-glucosaminidase and its isoenzymes in smoking and non-smoking workers at copper foundry occupational co-exposed to arsenic cadmium and lead]. / Aktywnosc N-acetylo-beta-D-glukozaminidazy i jej izoform w moczu palacych i niepalacych pracowników huty narazonych zawodowo na arsen, kadm i olów.

The kidneys are the critical organs in the case of a long-term occupational or environmental exposure to heavy metals and tobacco smoke. In diagnostics of renal damage useful are the methods which determine the activity of renal enzymes, quantify in urine (e.g. beta-glucuronidase, N-acetyl-beta-D-glucosaminidase). N-acetyl-beta-D-glucosaminidase (NAG) is one of the most often determined factors of tubular damage, since its activity increases in early stages of renal injury, ahead of appearance of excretory dysfunction. The aim of this research was to assess the influence of occupational exposure of copper-foundry workers to heavy metals (arsenic, cadmium, lead) on total activity of N-acetyl-beta-D-glucosaminidase and its molecular forms in urine. The investigated group was made up of 95 founders (smokers n = 51, non-smokers n = 44) and 43 people in control group (smokers n = 16, non-smokers n = 27). The concentrations of arsenic (As) and cadmium (Cd) were determined in urine, whilst the level of lead (Pb) was determined in whole blood. The activities of NAG and its isoforms were determined in urine. Smoking and non-smoking founders' urine demonstrated 14 times higher concentrations of arsenic levels in comparison with smoking and nonsmoking control group. Cadmium concentrations were 3.5 times higher in urine of smoking founders in comparison with smoking control group and about 3 times higher in case of nonsmoking founders in comparison with non-smoking control group. 7 times increase of lead concentration was observed in the whole blood within the smoking founders group in comparison with the smoking control group. In the blood of non-smoking founders was demonstrated about 10 times increase of lead concentration in comparison with the non-smoking control group. About 3-times increase of total NAG's activity was observed in urine of smoking founders and 4-times increase of non-smoking founders in comparison with smoking and non-smoking control group. The highest activity of NAG-B was observed in urine of smoking founders (11.35 +/- 7.85 U/g creatinine), then non-smoking founders (9.7 +/- 8.75 U/ g creatinine). It was confirmed, that the activity of N-acetyl-beta-D-glucosaminidase is a good factor in the assessment of occupational exposure to heavy metals like arsenic, cadmium and lead.

The concentration of selected cancer markers (TPA, TPS, CYFRA 21-1, CEA) in workers occupationally exposed to arsenic (As) and some heavy metals (Pb, Cd) during a two-year observation study.

OBJECTIVE: Molecular epidemiology studies have lately been focused on occupational cancer associated with exposure to chemical carcinogens in work environment. Measuring serum levels of tumour markers ie. the substances produced in transformed cells, is a modern method used in the prevention or early detection of cancer. A two-year observation study was constructed to investigate the relationship between arsenic, lead, and cadmium concentrations and the levels of cancer markers: TPA (tissue polipeptide antigen), TPS (tissue polipeptide specific antigen), and CYFRA 21-1 in 69 male workers occupationally exposed to As and Pb, and environmentally exposed to Cd via tobacco smoking. RESULTS: Significant correlations were found between CEA and blood Cd concentrations or between CEA and period of work under exposure. Multiple regression tests revealed also relationships between some cancer markers and the work period, and thereby the lifetime exposure to heavy metals. Duration of work under exposure significantly influenced TPA and TPS concentrations in these models. All the metals examined were found to have influence on the concentration of cancer markers, except for CYFRA 21-1, but the direction of this influence varied. Lead (especially FEP level) and cadmium were also among the metals affecting TPA concentration profile, although the multiple regression ratio for Cd-TPA correlation was negative. CONCLUSIONS: The strong positive correlation between blood concentrations of Cd and CEA, the marker of abnormal cellular differentiation, may reflect neoplastic transformation of normal cells stimulated by some carcinogens (e.g. cadmium). All the examined carcinogenic, or potentially carcinogenic metals (As, Cd, Pb) belong to the group of factors having impact on serum TPS and/or TPA concentrations in exposed workers. No correlation was found between CYFRA 21-1 and any metal studied but it is plausible that changes in the concentration level of this marker might be revealed after a longer observation period.

[Secondary nephropathies in occupational health practice. I. Secondary nephropathies due to occupational exposure]. / Nefropatie wtórne w praktyce lekarza medycyny pracy. I. Nefropatie wtórne w przebiegu narazenia zawodowego.

Kidneys are particularly susceptible to the effect of toxic agents that can cause renal damage and even renal failure. The aim of this study was to present current knowledge of the influence of occupational toxic agents on renal functions. The authors describe the major nephrotoxic factors, such as heavy metals (including lead, cadmium, and mercury), organic solvents, pesticides and silica. They discuss changes in the kidney structure and molecular mechanisms of nephrotoxicity and carcinogenesis induced by occupational exposure to major toxic agents and also indicate possibilities of detecting the predicted nephrotoxicity symptoms so that clinical, overt renal insufficiency could be prevented.

[Secondary nephropathies in occupational health practice. II. Kidney disorders induced by drug and contrast media]. / Nefropatie wtórne w praktyce lekarza medycyny pracy. II. Nefropatie wtórne w przebiegu stosowania srodków leczniczych i diagnostycznych.

Nowadays, drug induced kidney disorders have become a frequent health problem. Iatrogenic nephropathies are manifested by a wide variety of clinical symptoms, including acute renal failure (about 20%), one of the major negative prognostic factors in internal diseases. Occupational kidney disorders induced by exposure to chemical toxins at a work place may coincide with those caused by drugs. This comorbidity can increase the risk of their progression to further deterioration of renal function, leading finally to long lasting work disability among employees. In this paper, we analyzed the mechanism by which major nephrotoxic drugs (e.g., antibiotics, non-steroidal anti-inflammatory agents, contrast media and angiotensin converting enzyme inhibitors) exert their effect on kidneys. Special attention was paid to over-the-counter medications, which are available in many countries, and thus are frequently abused by the working population. The early identification of non-occupational causes of kidney disorders helps avoiding accumulation of nephropathies of different origin, being of great practical value.

[Trials of casual treatment of silicosis]. / Próby leczenia przyczynowego pylicy krzemowej.

Silica-induced lung injury and the development of silicosis is one of the major occupational diseases. Accumulation and deposition of respirable dust containing silica mineral particles in the lung produces chronic lung disease characterized by granulomatous and fibrotic lesions. Knowledge of precise mechanisms, which induce this process is still limited, hence problems faced in the treatment of silicosis, especially the casual one. This article describes various trials of casual silicosis treatment with tetrandrine (Tet), isolated from the root of Stephania tetrandra, tumor necrosis factor (TNF) antagonists, polyvinyl-pyridine-N-oxide (PVNO), aluminum compounds, corticosteroids or bronchoalveolar lavage (BAL). The existing methods are not sufficient, which warrants further investigations. At present, prevention of the disease and treatment of its complications are most important.

[Distribution of conduction velocity in the ulnar nerve among lead exposed workers]. / Rozklad predkosci przewodzenia we wlóknach nerwu lokciowego u osób zawodowo narazonych na dzialanie olowiu.

BACKGROUND: Neuropathy can be one of the symptoms of the toxic effect of lead on the nervous system. The aim of this work was to perform clinical and neurophysiological assessment of the peripheral nervous system in workers exposed to lead. MATERIALS AND METHODS: The study included 34 exposed workers and 20 healthy controls. Motor (ulnar, peroneal) and sensory (ulnar, sural) conduction velocity as well as conduction velocity distribution in ulnar n. and EMG from the I. interosseus muscle were assayed. The whole blood value of Pb 400 microg/l was adopted as a borderline between workers with low and increased blood lead concentrations. The FEP value of 70 microg/100 ml erythrocytes was the borderline between those without or with biochemical signs of Pb loading. The workers' age and duration of occupational exposure did not differ significantly between the study and control groups. RESULTS: None of the workers showed clinical signs of neuropathy or abnormalities in routine neurographic examination. As compared with controls, a significantly lowered conduction in slow-conducting motor fibers and neurogenic changes in EMG were observed in workers with the whole blood Pb concentration over 400 microg/l and in workers with FEP level over 70 tig/100 ml erythrocytes. CONCLUSION: Neurotoxic effect of Pb on peripheral nerves is manifested by the damage of slow-conducting motor nerves fibers when overt neuropathy is not yet visible.

[The influence of occupational exposure to arsenic and heavy metals on the activity of catepsins and their inhibitors in blood serum of copper smelters]. / Wplyw zawodowego narazenia na arsen i metale ciezkie na aktywnosc katepsyn i ich inhibitorów w surowicy krwi pracowników huty miedzi.

BACKGROUND: Exposure to arsenic, lead, and cadmium poses the risk of cancer. Cathepsins (CP) and their natural inhibitors (CPI) in blood serum are markers of carcinogensis. The aim of this work was to verify the existence of relationships between the exposure to the airesaid elements and the activity of CP and CPL. MATERIALS AND METHODS: The levels of Pb and Cd in blood, Mn, Cu, Zn, Ca, Mg, Fe, Se CP as well as free and bound CPI in serum, FEP in erythrocytes, and As in urine were measured in 186 production workers of Legnica Copper Smelter (study group) and 56 administrative employees (control group) and then analyzed. RESULTS: CF levels were significantly elevated in both groups and CPI levels were elevated in the study group vs. the control group. There were no statistically significant relationships between CF and CPI levels and the remaining parameters in the study group. whereas they were found for CPI in the control group. The results indicate that occupational and environmental exposures to toxic metals (arsenic, lead, cadmium) may lead to the elevated levels of CF and CPI. CONCLUSIONS: The obtained results support the assumptions of the study.

Some aspects of arsenic toxicity and carcinogenicity in living organism with special regard to its influence on cardiovascular system, blood and bone marrow.

This paper gathers data on the most current aspects of arsenic action, especially its influence on the cardiovascular system, blood and bone marrow. A potential carcinogenic mechanism of arsenic is also discussed. Arsenic is a potent toxicant that may exist in several valencies and in a number of inorganic and organic forms. Most cases of arsenic-induced toxicity in humans are due to exposure to inorganic arsenic, and there is an extensive database on the human health effects of common arsenic oxides and oxyacids. Exposure of humans living near hazardous waste sites may involve inhalation of arsenic dusts in the air, ingestion of arsenic in water, food or soil, or dermal contact with contaminated soil or water. The exposure to arsenic via the inhalation route is responsible for the increased risk of lung cancer, although respiratory irritation, nausea and skin effects may also occur. The oral route of exposure to arsenic predominates in the general population. The most common effects of arsenic ingestion are gastrointestinal irritation, peripheral neuropathy, vascular lesions, anemia, skin diseases, including skin cancer and other cancers of the internal organs like bladder, kidney, liver or lung. Relatively little information is available on the effects of direct dermal contact with inorganic arsenicals, but several studies indicate local irritation and dermatitis as the major ones.

Relation between heavy metals and left ventricular diastolic function in patients with coronary artery disease.

One of the earliest detectable abnormalities in patients with coronary artery disease is left ventricular diastolic dysfunction. Its main cause is myocardial ischaemia, but still many of other mechanisms are possible. The aim of this study was to investigate the relation of cadmium, lead, copper, zinc, and selenium with left ventricular diastolic function indices in patients with coronary artery disease. The study included 33 patients (14 with single-vessel disease and 19 with multivessel disease on angiography) who were not exposed occupationally to heavy metals. Control group consisted of 18 patients with normal coronary arteries. The blood cadmium and lead concentrations and serum zinc, selenium and copper concentrations were determined using atomic absorption spectrophotometry. Left ventricular diastolic function parameters were estimated by echo-Doppler and colour M-mode. All heavy metal concentrations were within the standard ranges in all studied groups. Patients with single-vessel disease, multivessel disease and control group did not differ in concentrations of studied metals. On univariate and multivariate analysis only cadmium significantly correlated with echocardiographic parameters of left ventricular diastolic function: peak early to peak late mitral inflow velocity ratio (r = -0.36, p < 0.05) and deceleration time of early mitral inflow (r = 0.43, p < 0.01) in patients with CAD. No significant correlations between concentrations of heavy metals and indices of left ventricular diastolic function were found in control group. The present data suggest that cadmium in concentrations even below the threshold limit value for unexposed population may contribute to development of left ventricular diastolic dysfunction in patients with CAD, potentializing the effect of myocardial ischaemia.

[Plasma concentration of selected neoplastic markers in persons occupationally exposed to arsenic and heavy metals]. / Analiza stezen wybranych markerów neoplazmatycznych u osób zawodowo narazonych na arsen i metale ciezkie.

BACKGROUND: Industrial development increases the threat to human health caused by chemical contamination of the environment. Occupational neoplasms induced by exposure to carcinogenic factors present in workplaces are one of its effects. Heavy metals, especially arsenic, play an important role in this process. The aim of the study was to assess potential carcinogenic effects of arsenic and other heavy metals and the relation between their concentrations in organic fluids and the level of specific neoplastic markers, which might indicate the risk of the development of occupation-related neoplastic diseases. MATERIALS AND METHODS: Over two years, 224 men employed in the "Legnica" Copper Foundry, Divisions of Furnace Charge Preparing and Metallurgy, were examined. Plasma and urine concentrations of some metals and neoplastic markers were measured. We analyzed a possible correlations between metals and markers concentrations. RESULTS AND CONCLUSIONS: The study allowed to establish a strong positive correlation between urine arsenic concentration, blood cadmium concentration and some serum neoplastic markers (CEA, SCC-Ag, PSA). There was a distinct synergistic reaction between the levels of arsenic, cadmium and lead intoxication and the number of smoked cigarettes, so that smoking copper smelters exposed to these metals form a high cancer risk group. Significant positive correlation between blood lead concentration, free erythrocyte protoporphyrins and the level of arsenic in copper smelters might indicate the increased risk of late effects of intoxication in persons under combined exposure to these metals.

[The effect of occupational exposure to heavy metals and arsenic on serum concentrations of carotenoids in copper foundry workers]. / Wplyw ekspozycji zawodowej na olów i arsen na stezenie karotenoidów w surowicy u pracowników huty miedzi.

BACKGROUND: The aim of the project was to analyze the effect of occupational exposure to heavy metals on the efficiency of antioxidative defensive mechanisms, represented by the concentration of carotenoids (KTND) in serum. MATERIALS AND METHODS: The study involved 96 workers exposed to heavy metals in a copper foundry. Two subgroups of workers--those exposed only to lead and those to the combination of lead and arsenic--were analyzed. The control group consisted of 81 subjects not exposed to heavy metals. We measured concentrations of lead and cadmium in whole blood, selenium, manganese, copper, zinc, calcium, magnesium and carotenoids in serum, arsenic in urine and free erythrocyte protoporphyrin (FEP). RESULTS: Serum carotenoids concentration was significantly lower in workers exposed to heavy metals than in the control group (48.76 +/- 15.32 vs. 68.36 +/- 21.46 microg/dl; p < 0.001). There were no significant differences between serum concentrations of carotenoids in the subgroup exposed only to lead and the subgroup exposed to both lead and arsenic ((48.62 +/- 16.64 vs. 48.86 +/- 14.41 microg/dl). We found significant positive correlation between blood cadmium levels and serum carotenoids in the control group (r = -0.3406, p < 0.05). In the multiple regression analysis (optimal model), there was significant negative influence of blood lead on serum KTND levels and positive influence of blood cadmium on serum KTND concentrations in the subgroup of workers exposed only to lead (R(2) A = 0.9102; p < 0.001). In smelters exposed to both lead and arsenic, we observed significant negative influence of FEP and positive influence of arsenic on KTND concentrations in serum in the optimal model of multiple regression (R(2) A = 0.9249; p < 0.001). CONCLUSIONS: Occupational exposure to lead and arsenic in moderate doses affects serum carotenoids concentration in exposed humans.

[Subclinical lead neuropathy]. / Subkliniczna neuropatia olowicza.

AIM: The electrophysiological assessment of peripheral nervous system in asymptomatic workers chronically exposed to inorganic Pb. MATERIAL AND METHODS: 41 asymptomatic workers (group A and B) and 35 healthy subjects (group C) were included in study. Motor (radial, peroneal), and sensory (radial, sural) nerves conduction studies, EMG from Extensor Digitorum Communis (EDC) muscle, and skin sympathetic response (SSR) were performed. The level of free erythrocyte protoporphyrins (FEP) was measured in workers. The value of 100 microg/100 ml of erythrocytes was the borderline between these without (A) and those with (B) biochemical signs of Pb loading. Age and duration of occupational exposure did not differ between 2 groups of workers. RESULTS: In motor conduction studies only amplitude of muscle action potential from radial nerve in group B was significantly lower when compared with controls. Parameters describing sensory studies did not differ significantly among 3 groups. In both groups of workers EMG revealed neurogenic changes in EDC muscle, and duration of motor unit potential was correlated with FEP's level. The amplitude of SSR was in both groups of workers significantly lower in comparison with results obtained in controls. Moreover, there was a negative correlation between amplitude of SSR obtained from hand with FEP's level. CONCLUSIONS: In asymptomatic workers chronically exposed to inorganic PB the subclinical damage of peripheral nervous system involving neurogenic changes on EMG and abnormal SSR was recorded.

Metabonomic analysis of serum of workers occupationally exposed to arsenic, cadmium and lead for biomarker research: a preliminary study.

Environmental metabonomics is the application of metabonomics to characterize the interactions of organisms with their environment. Metabolic profiling is an exciting addition to the armory of the epidemiologist for the discovery of new disease risk biomarkers and diagnostics. This work is a continuation of research searching for preclinical serum markers in a group of 389 healthy smelter workers exposed to lead, cadmium and arsenic. Changes in the metabolic profiles were studied using Proton Nuclear Magnetic Resonance Spectroscopy on pooled serum samples from both the metal exposed and control groups. These multivariate metabonomic datasets were analyzed with Principal Component Analysis and Partial Least Squares Discriminant Analysis. Analysis of metabolic profiles of people exposed to heavy metals suggests energy metabolism disturbance induced by heavy metals. Changes in lipid fraction (very-low-density lipoprotein - VLDL, low-density lipoprotein - LDL), unsaturated lipids and in the level of amino acids suggest perturbation of the metabolism of lipids and amino acids. This study illustrated the high reliability of NMR-based metabonomic profiling on the study of the biochemical effects induced by the mixture of heavy metals. This approach is capable of identifying intermediate biomarkers of response to toxicants at environmental/occupational concentrations, paving the way to its use in a monitoring of smelter workers exposed to low doses of lead, cadmium and arsenic.

Application of classic epidemiological studies and proteomics in research of occupational and environmental exposure to lead, cadmium and arsenic.

The metals/metaloids lead (Pb), cadmium (Cd), and arsenic (As) are among the leading toxic agents in the environment. They represent an important source of dangerous exposure in humans, particularly in industry workers. The most serious consequences of exposure to those heavy metals are cancers and cardiovascular diseases. In studies of human exposure to Pb, Cd, and As alone and in a mixture markers signaling the subtle, early lesions that occur in the human body are still lacking. It is appropriate to develop high throughput techniques and use non-invasive materials. The techniques currently used in classic epidemiological studies allow selection of single markers of changes of exposure to chronic low dose levels of metal/metaloids mixtures. However, application of proteomic techniques in such studies may allow the selection of new biomarkers of environmental and occupational exposure to heavy metals characterized by high sensitivity and specificity. As presented in our review paper, proteomic techniques in combination with appropriate statistical methods allow the selection of potential markers to estimate the changes in the human body when exposed to those heavy metals.

Relation between occupational exposure to lead, cadmium, arsenic and concentration of cystatin C.

UNLABELLED: Lead, cadmium and arsenic represent well recognized toxic agents which in a specific manner disturb function of cardiovascular system. Cystatin C has been accepted to be a significant prognostic factor for cardiovascular diseases. The study aimed at defining relationship between occupational exposure to lead, cadmium and arsenic on one hand and concentration of cystatin C on the other. The studies were performed on 282 men occupationally exposed to lead, cadmium and arsenic. Among the tested individuals several groups of persons were distinguished: exposed exclusively to lead (Pb group), cadmium (Cd group), arsenic (As group), to lead and cadmium (Pb/Cd group), to lead and arsenic (Pb/As group) or to cadmium and arsenic (Cd/As group). In all the individuals serum concentration of cystatin C was estimated. Concentration of cystatin C was found to be significantly higher in Pb group than in Cd and As groups, also in Pb/Cd group higher than in Cd group and in Pb/As group than in As group. Positive linear correlations were established between Pb concentration in blood (Pb-B) and serum concentration of cystatin C (r=0.59; p<0.05) as well as between urinary concentration of As (As-U) and serum concentration of cystatin C (r=0.41; p<0.05). Regression analysis demonstrated that higher blood level of lead, higher urinary level of arsenic, more advanced age and higher body mass index represented independent risk factors of an increased serum concentration of cystatin C in the group of persons exposed to lead, cadmium and arsenic. CONCLUSIONS: Higher blood level of lead and higher urinary level of arsenic represented independent risk factors of an increased serum concentration of cystatin C in the group of persons occupationally exposed to lead, cadmium and arsenic. Concentration of lead in blood was significantly influencing serum concentration of cystatin C. The highest mean serum concentration of cystatin C was detected in the group of foundry workers exposed simultaneously to lead and arsenic.