Lack of reversal effect of EDTA treatment on cadmium induced renal dysfunction: a fourteen-year follow-up

The aim of this study was to evaluate the effect of ethylenediaminetetraacetic acid (EDTA) on cadmium (Cd) induced renal dysfunction. Seventeen workers (14 males, 3 females) were diagnosed with occupational Cd poisoning in 1986. These individuals had between 7 to 39 years of Cd exposure. From 1986 to 1999, patients received periodic EDTA therapy as part of their follow-up, all at the same hospital. Levels of urinary cadmium (UCd) and urinary beta2-microglobulin (B2M) were measured before and after each annual EDTA treatment period. Renal dysfunction was defined as urinary B2M > 0.8 mg/g Cr (creatinine). In these workers, patients with UCd level higher than 10 microg/g Cr in 1986 had abnormal B2M excretions (> or = 0.8 mg/g Cr) or trended to have abnormal B2M levels during the treatment period. However, in subjects with UCd concentration lower than 10 microg/g Cr in 1986, their urinary B2M excretions either remained normal (< 0.8 mg/g Cr) or returned to normal during the treatment period. The prevalence of renal dysfunction increased during the follow up period regardless of whether UCd levels increased or not, indicating a progressive renal dysfunction despite removal from Cd exposure. Our results suggest that reversibility of renal dysfunction caused by Cd related to the level of Cd exposure at the time of removal from exposure: renal dysfunction could be reversed if initial UCd < 10 microg/g Cr, but was irreversible when UCd > 10 microg/g Cr. Repeated examinations on these 17 Cd exposed workers from 1986 to 1999 also revealed that periodic administration of EDTA had no beneficial effects on chronic Cd-induced renal dysfunction.     

Cadmium biomonitoring and renal dysfunction among a population environmentally exposed to cadmium from smelting in China (ChinaCad)

Cadmium, an environmental pollutant, can have adverse effects on the human body. The kidney is the critical organ. In order to improve the understanding of the dose-response relationship between cadmium exposure and health effects, and especially renal dysfunction, a study on a general population group in China was performed. This study was therefore concerned with cadmium exposure biomarkers, such as the concentrations in blood (BCd) and urine (UCd), and effect biomarkers of renal dysfunction, such as ₂-microglobulin (₂m), retinol binding protein (RBP) and albumin (ALB). To improve the evaluation of exposure levels in relation to the adverse health effects of cadmium exposure in the general population, a quality control program was conducted to determine analytical quality in the determination of cadmium in blood and urine and for ₂m, creatinine, ALB and RBP. The measurements showed that analytical quality was adequate. The exposure and effect biomarkers were studied in the population groups living in three areas, namely a control area and two Cd polluted areas. In the highly exposed area, most of the BCd values were higher than 5 g/l and most of the UCd values were higher than 5 g/g creatinine. ₂-microglobulin, retinol binding protein, and albumin in urine were all significantly higher in the population living in the heavily polluted area than in that in the control area. Based on data from all three areas, a marked dose-response relationship between UCd or BCd and the prevalence of renal dysfunction was demonstrated. The number of abnormalities in kidney was related to the level of cadmium exposure. Only one index of renal tubular dysfunction was affected in subjects exposed to low levels of cadmium, but more than two indices of renal function were affected in those exposed to high levels.     

Concentration of Thyrotropic Hormone in Persons Occupationally Exposed to Lead,Cadmium and Arsenic

Thyroid hormones are essential for body homeostasis. The scientific literature contains restricted proofs for effects of environmental chemical factors on thyroid function. The present study aimed at evaluating the relationship between toxicological parameters and concentration of thyrotropic hormone in persons occupationally exposed to lead, cadmium and arsenic. The studies were conducted on 102 consecutive workers occupationally exposed to lead, cadmium and arsenic (mean age 45.08 ± 9.87 years). The estimated parameters characterizing occupational exposure to metals included blood cadmium concentration (Cd-B), blood lead concentration (Pb-B), blood zinc protoporphyrin concentration (ZnPP) and urine arsenic concentration (As-U). Thyroid function was evaluated using the parameter employed in screening studies, the blood thyrotropic hormone concentration (TSH). No differences were disclosed in mean values of toxicological parameters between the subgroup of persons occupationally exposed to lead, cadmium and arsenic with TSH in and out of the accepted normal values. Logistic regression demonstrated that higher blood total bilirubin concentrations (ORu = 4.101; p = 0.025) and higher Cd-B (ORu = 1.532; p = 0.027) represented independent risk factors of abnormal values of TSH in this group. In conclusion, in the group of workers exposed to lead, cadmium and arsenic, higher blood cadmium concentration seems to augment the risk of abnormal hormonal thyroid function.     

Environmental cadmium exposure and forearm bone density

Environmental exposure to cadmium may give rise to osteomalacia combined with renal dysfunction, so called 'Itai-Itai disease', which was endemic in the heavily polluted area in Japan. The main focus of this study was to investigate whether environmental exposure to cadmium is associated with low bone mass in a population living near a smelter. A total of 790 persons (302 males and 488 females), who were all over 35 years old and resided in areas near a lead, zinc and cadmium smelter and in a control area in southeast China, completed a questionnaire, and bone mineral density was measured by SPA-4 single photon absorptiometry at the radius and ulna. Cadmium content of urine was determined by graphite-furnace atomic absorption spectrophotometry as a measure of dose. The present study shows that forearm bone densities were negatively correlated with urinary cadmium excretion (p < 0.001) and forearm bone density decreased linearly with age (p < 0.001) and urinary cadmium (p < 0.01), suggesting a dose-effect relationship between cadmium dose and bone mineral density. Based on the World Health Organization criteria, (bone mineral density < -2.5 SDs below the normal young adult), the prevalence of osteoporosis in women increased from 34.0% in the control area to 51.9% in the heavily polluted area (p < 0.01) among subjects over 50 years old, and the odds ratio value was 2.09 (95% CI: 1.08-4.03) for the highly polluted area compared with the control area. A striking observation in the study was a marked increase of the prevalence of fracture in the cadmium-polluted area in both sexes. It was concluded that environmental exposure to cadmium is associated with an increased loss of bone mineral density in both gender, leading to osteoporosis and increased risk of fractures, especially in the elderly and in females.     

Cadmium, osteoporosis and calcium metabolism

Occupational exposure to cadmium has for long been associated with renal tubular cell dysfunction, osteomalacia with osteoporosis, hypercalciuria and renal stone formation. High environmental exposure in Japan resulting from a stable diet of cadmium contaminated rice caused itai-itai disease, fractures occurring mainly in elderly multiparous women, with a form of osteomalacia, osteoporosis and renal dysfunction. More recently a population based study in Europe, in the vicinity of zinc smelters has shown that low to moderate exposure to cadmium, with a mean urinary excretion of cadmium of the order of 1 microg/g creatinine has been associated with a decrease in bone density, an increased risk of bone fractures in women and of height loss in men. In a population-based study of residents near a cadmium smelter in China, forearm bone density was shown to decrease linearly with age and urinary cadmium in both sexes, suggesting a dose effect relationship between cadmium dose and bone mineral density. A marked increase in the prevalence of fractures was shown in the cadmium-polluted area in both sexes. Concentrations of cadmium in blood and urine were taken as exposure biomarkers, and beta2-microglobulin, retinol binding protein and albumin as biomarkers of effect. A marked dose response relationship between these indicators of exposure and effect was shown. Hypercalciuria, which may progress to osteoporosis, has been taken as a sensitive renal-tubular biomarker of a low level of cadmium exposure. Cadmium may also act directly on bone. Animal studies have shown cadmium to stimulate the formation and activity of osteoclasts, breaking down the collagen matrix in bone. Osteoporosis is the main cause of fracures in post-menopausal women, a common occurrence worldwide, giving rise to disability and a high cost to health services. The identification of cadmium, an environmental pollutant, as one causal factor is highly significant in helping to control the incidence of this complex condition.     

Assessment of genome damage in occupational exposure to ionising radiation and ultrasound

The mutagenic effects of low doses of radiation on occupationally exposed subjects were studied on lymphocyte culture using two methods: analysis of structural chromosome aberrations and micronucleus assay. The results obtained in subjects exposed to ionising radiation alone were compared to those exposed to both ionising radiation and ultrasound. A correlation between the total number of chromosome aberrations and distribution of micronuclei in the genome of somatic cells show higher deviation in the group exposed to X-ray and ultrasound than in the group exposed to X-rays alone. The degree of genome damage in occupational exposure to X-rays and ultrasound were discussed.     

Environmental epidemiological study and estimation of benchmark dose for renal dysfunction in a cadmium-polluted area in China

We have performed a study aimed at investigating the critical concentration of urinary cadmium (UCd) required for the development of renal dysfunction. We studied population groups (totally 790 persons) living in two cadmium exposed areas and one control area in China. UCd, was determined as an indicator of cadmium exposure and accumulation, while the concentrations of N-acetyl-beta-D-glucosaminidase (NAG), its iso-form B (NAG-B), beta2-microglobulin (B2M), retinol binding protein (RBP), and albumin (ALB) in urine were measured as indicators of the renal effects caused by cadmium. There was a significantly increased prevalence of hyperNAGuria, hyperNAG-Buria, hyperB2Muria, hyperRBPuria and hyperALBuria with increasing levels of Cd excretion in urine. We used the benchmark dose (BMD) procedure to estimate the critical concentration of urinary cadmium in this general population. The lower confidence limit of the BMD (LBMD-05) of urinary cadmium for a 5% level of risk above the background level was estimated for each of the renal effect indicators. The BMD-05/LBMD-05 were estimated to be 4.46/3.99, 6.70/5.87, 8.36/7.31, 7.98/6.98 and 15.06/12.18 microg/g creatinine for urinary NAG-B, NAG, B2M, RBP and ALB, respectively. Our findings suggest, based on the present study, that the Lower Confidence Limit of the Population Critical Concentration of UCd (LPCCUCd-05) of tubular dysfunction for 5% excess risk level above the background may be ca. 3-4 microg/g creatinine, and that cadmium concentration in urine should be kept below this level to prevent renal tubular damage. This report is the first to use the BMD method in this field and to define the concept of critical concentration in urine.     

Tissue cadmium (Cd) concentrations of people living in a Cd polluted area, Japan

There are more than 50 cadmium (Cd) polluted areas in Japan. The severest general environmental Cd polluted area in Japan was the Jinzu River basin in Toyama Prefecture where Itai-itai disease had been endemic. The present study aimed to compare organ Cd concentrations of inhabitants who had been exposed to different levels of environmental Cd and to clarify the health effects of the environmental Cd exposure in Japan. Since 1960 we have measured tissue Cd concentrations of inhabitants with a history of living in a different Cd polluted areas. Study population living in Cd polluted areas were 36 (1 male, 35 females) patients with Itai-itai disease, 20 (7 males, 13 females) subjects suspected of having Itai-itai disease, 8 (2 males, 6 females) inhabitants in Cd polluted areas other than the Jinzu River basin. Subjects who had lived in Cd non-polluted area were 72 inhabitants. Cd concentrations in liver, pancreas and thyroid of those living in Cd polluted areas were as high as those of patients with Itai-itai disease, and their Cd concentrations in renal cortex were as low as those of patients with Itai-itai disease. The present study demonstrated that tissue Cd concentrations of some inhabitants in Cd polluted areas other than Jinzu River basin are equal to those of the patients with Itai-itai disease and that patients with Itai-itai disease were present even in these areas.     

Repair competence assay in studies of the influence of environmental exposure to c-PAHs on individual susceptibility to induction of DNA damage

Previous results from studies performed in three European cities suggested a decrease in DNA repair efficiency observed in lymphocytes of subjects occupationally exposed to environmental carcinogenic polycyclic aromatic hydrocarbons (c-PAHs). The aim of this study was to investigate whether a relationship between exposure to environmental c-PAHs and cellular vulnerability to the induction of DNA damage and its repair is confirmed in a pooled group of subjects from Prague, Košice and Sofia. The investigated pool consisted of 144 subjects occupationally exposed to environmental c-PAHs, who were municipal policemen or bus drivers. A control group of 115 matched individuals consisted of males unexposed at work to c-PAHs. The repair efficacy was evaluated by a comparison of the DNA damage detected by the single cell gel electrophoresis (SCGE) immediately after challenging the cells with X-ray irradiation, with residual damage (RD) being measured after an incubation period of 60 min. A stochastic concept for a mechanism of the interaction between DNA and various genotoxic exposures, was applied to analyze a relationship between exposure and biological effect in the studied sample. The outcome of the study confirms that the exposure to environmental c-PAHs or smoking cigarettes, significantly decreases DNA repair efficiency (repair efficiency in the pooled group of exposed individuals was 61.8 ± 11.8% versus 67.9 ± 9.9 in control, p < 0.001, and repair efficiency in group of smoking individuals was 63.0 ± 11.5% versus 65.9 ± 11.1 in nonsmokers, p < 0.005). The repair efficiency can be affected by a genetic polymorphism, such as subjects with a homozygous mutation in polymorphic CYP1A1_(Val/Val) enzyme, or slow NAT2 acetylators, who showed a considerably lower DNA repair efficiency (i.e. average repair efficiency in subgroups of fast acetylators was for the control subgroup 68.1% versus 66.5% in exposed subjects, while in the case of subgroups of slow acetylators, for the control group was 68.0% versus significantly less in the exposed subjects, 60.6%, p < 0.05). Smoking habits, or the diet's vitamin content, significantly affected the process. The results obtained confirm a potential value of the method as a biomarker of susceptibility in molecular epidemiology or preclinical studies, aimed at predicting susceptibility to various genotoxic exposures (environmental, occupational, therapeutic). To conclude, the research proved the influence of environmental c-PAHs, genotypes, and life styles on DNA damage and on its repair efficiency. Even low exposure to environmental c-PAHs altered DNA repair abilities of the subjects, which may result in an increased cancer risk. The findings confirm that c-PAHs should become pollutants that are subject to regulation.     

Study of the cytogenetic effects of occupational exposure to pesticides on sanitation workers in Belo Horizonte, Brazil

Sanitation workers handling pesticides in the control of disease vectors constitute an occupationally exposed population to genotoxic substances. The aim of the present study was to investigate the relation between the occupational exposure to various pesticides and the presence of cytogenetic damage. Fifty-nine men were selected (29 sanitation workers and 30 control individuals) with ages varying between 18-57 years who lived and worked in the same area in Belo Horizonte (Brazil). The following parameters were determined for all individuals using the cytokinesis-block micronucleus (MN) assay in peripheral blood lymphocytes: MN/1000 binucleated cells (BC), BC with MN (BCMN)/1000 BC, nucleoplasmic bridges (NB)/1000 BC, apoptotic and necrotic cells/500 cells and nuclear division index. The analysis of covariance showed significantly higher (p < 0.05) mean frequencies of MN (15.81 +/- 1.31 vs 4.71 +/- 0.42), BCMN (15.10 +/- 1.22 vs 4.62 +/- 0.44), NB (4.59 +/- 0.76 vs 1.00 +/- 0.34), and necrotic cells (12.07 +/- 1.45 vs 5.17 +/- 0.70) in the exposed group when compared to the control group. There was no significant difference in the apoptotic cell frequency between the two groups, while the nuclear division index was significantly lower (1.49 +/- 0.02 vs 1.61 +/- 0.02) in the control group. Neither the time of exposure nor the smoking or alcohol drinking habit influenced the cytogenetic parameters examined. According to these results, occupational exposure to pesticides induced genotoxic and cytotoxic effects in sanitation workers.     

Prevalence of kidney dysfunction in humans – Relationship to cadmium dose, metallothionein, immunological and metabolic factors

Long term cadmium (Cd) exposure in occupational and general environments may give rise to kidney dysfunction. This effect is usually considered to be the critical effect, i. e. the effect that occurs at relatively low level of exposure. The present review focused on studies of the prevalence of cadmium-related kidney dysfunction among population groups residing in cadmium contaminated areas in China. Dose–response relationships were shown between UCd and the prevalence of increased levels of biomarkers in urine of renal tubular dysfunction such as urinary beta-2-microglobulin or N-acetyl-beta-d-glucosaminidase – NAG or urinary albumin, a biomarker of glomerular kidney dysfunction. Factors that influence these dose–response relationships include: 1) Metallothionein mRNA levels in peripheral blood lymphocytes, used as a biomarker of the ability of each person, to synthesize metallothionein (a protein known to provide intracellular protection against cadmium toxicity). 2) The occurrence of increased levels in blood plasma of autoantibodies against metallothionein. 3) Concomitant changes in glucose metabolism i e Type II diabetes. 4) Concomitant exposure to other nephrotoxic agents such as inorganic arsenic. Increased susceptibility in diabetics has been shown also in population groups in Europe. In persons with type II diabetes and increased levels of autoantibodies against metallothionein in blood plasma or in persons with concomitant exposure to environmental inorganic arsenic, indications of Cd-related kidney dysfunction was observed at UCd levels around 1 μg/g creatinine, levels found among “unexposed” population groups in many countries.     

PAH-DNA adducts in a Chinese population: relationship to PAH exposure, smoking and polymorphisms of metabolic and DNA repair genes.

The present study was conducted in a Chinese population to evaluate the usefulness and sensitivity of PAH-DNA adduct as a biomarker of PAH exposure, and to examine the potential effects of smoking and polymorphisms of responsive genes on DNA adduct formation induced by PAH exposure. The polymorphisms of genes examined include GSTM1, GSTT1, CYP1A1, microsomal epoxide hydrolase (mEH) and excision repair cross-complementary group 2 (ERCC2). A total of 194 subjects with a broad range of PAH exposures were recruited, including 116 occupationally exposed workers, 49 metropolitan residents and 29 suburban gardeners. A significant exposure-response relationship was observed between PAH exposure and DNA adducts in leukocytes across the entire group of subjects (p < 0.0001). The levels of PAH-DNA adducts in the subgroup with lowest occupational exposure to PAHs (< 0.1 microg BaP m(-3)) was significantly higher than that in metropolitan residents and suburban gardeners. However, no significant difference was detected between residents and gardeners, with mean BaP concentrations of 0.028 and 0.011 microg m(-3), respectively. The polymorphisms of genes examined failed to show significant effects on PAH-induced adduct formation except ERCC2 Lys751Gln genotypes. A significantly higher level of PAH-DNA adduct was found in subjects with wild-type ERCC2 than those who have either heterozygous or homozygous variant alleles (p < 0.01). Smoking, age and gender did not substantially contribute to PAH-induced DNA adduct formation in this study. The study suggests that PAH-DNA adducts may serve as a reliable biomarker of PAH exposure in occupational settings but may not be sensitive enough to be used in populations with environmental exposures to PAHs.     

Environmental exposure to cadmium and factors affecting trace-element metabolism and metal toxicity

In the general population, food constitutes the major environmental source of cadmium (Cd) in nonsmokers. It is established that leafy vegetables, roots, and grains (wheat or rice) can accumulate relatively high amounts of Cd from the soil. Beef liver and kidney and shellfish are also major dietary sources of Cd. The daily intake of Cd in various parts of the world is different and depends on both the dietary habits and concentration of Cd in foodstuffs. Because of the long biological half-life of Cd in humans and absence of any specific indicators of its toxicity, the environmental exposure of Cd should be monitored in various countries. Although environmental Cd poisoning is rare, there are isolated reports on excessive exposure to Cd in Japan and Shipham, a zinc-mining town in England. The body retention and toxicity of Cd depends on various factors, such as daily intake, the form of Cd in food, its interactions with essential elements, and nutritional status of the population. Since kidney is considered a critical organ in Cd toxicity, the indicators of renal dysfunction have been widely used for evaluation of Cd poisoning in occupationally exposed people. It is unclear whether similar indicators can be used for monitoring environmental Cd exposure.     

Kidney dysfunction and cadmium exposure--factors influencing dose-response relationships

Our early toxicological studies showed that metallothionein (MT) is a protein that carries cadmium (Cd) to the kidney, explaining why Cd exposures during long time periods may give rise to kidney dysfunction. This dysfunction is usually considered to be the critical effect, i.e. the adverse effect that occurs at the lowest exposure level. MT also provides intracellular protection against cadmium toxicity. In studies of population groups in cadmium contaminated areas in China, we investigated factors that affected the relationship between internal dose of Cd, as indicated by blood Cd (BCd) or urinary Cd (UCd), and the prevalence of kidney dysfunction. We found dose-response relationships between UCd and the prevalence of increased levels of biomarkers of renal tubular dysfunction (urinary beta-2-microglobulin, B2M, or N-acetyl-beta-d-glucosaminidase - NAG) or urinary albumin (UAlb), a biomarker of glomerular kidney dysfunction. Two years after Cd intake from contaminated rice was diminished, renal tubular dysfunction appeared unchanged or aggravated among those with higher UCd; Another 8 years later, i.e. 10 years after Cd intake was decreased, the prevalence of renal tubular dysfunction was still increased but UAlb had returned to normal. Factors that influenced the dose-response relationships were: (1) time after maximum exposure. (2) Concomitant exposure to other nephrotoxic agents such as inorganic arsenic. (3) Cd induced metallothionein mRNA levels in peripheral blood lymphocytes, used as a biomarker of the ability of each person, to synthesize MT. (4) The occurrence of increased levels in blood plasma of autoantibodies against MT. The two last points further support a role in humans of MT as a protective protein against tissue damage from cadmium and gives support to previous ideas developed partly in experimental systems.     

Exposure to environmental polycyclic aromatic hydrocarbons: influences on cellular susceptibility to DNA damage (sampling Kosice and Sofia)

The aim of this study was to investigate a possible influence of occupational exposure to carcinogenic environmental polycyclic aromatic hydrocarbons (c-PAHs) on cellular susceptibility to the induction of the DNA damage. Monitoring was performed and blood samples were collected from two groups of male subjects: occupationally exposed and matched controls. The group exposed to c-PAHs (average age of 35.1 years) consisted of 52 policemen from Košice and 26 policemen and 25 bus drivers (51 altogether) from Sofia. The control group (average age of 36.4 years) consisted of 54 unexposed subjects from Košice and 24 from Sofia. In the investigated groups 52.5% of exposed subjects and 45.3% of control were current smokers. A challenging dose of X-rays (3 Gy) and an alkaline version of the single cell gel electrophoresis (SCGE) assay, known as Comet assay, were used to evaluate levels of induced DNA damage and repair kinetics in isolated human blood lymphocytes. DNA damage detected in lymphocytes prior to or after irradiation did not differ significantly between exposed and unexposed subjects. A significant decrease in repair efficiency due to exposure to PAHs was observed in the exposed individuals from Košice and Sofia, when analysed separately or together. A negative influence of tobacco smoking on the efficiency of DNA repair was observed. Statistically significant differences were found between subgroups stratified according to education level in Sofia: the half times for DNA repair declined with the increasing level of education. These results confirm that environmental exposure to c-PAHs can alter the ability of blood lymphocytes to repair DNA damage and, as a result could potentially lead to effects that are hazardous to human health.     

Molecular biomonitoring of a population of nurses handling antineoplastic drugs

Many antineoplastic drugs have been found to have carcinogenic, mutagenic and teratogenic activity and so hospital personnel handling these substances are potentially exposed to health risk. Understanding this risk derived from protracted occupational exposure has great relevance even if the workers normally adopt individual and environmental protective measures. To address this question we have studied the presence of DNA and chromosome damage in a population of nurses employed in Italian oncology units and in matched controls. We used the comet assay to evidence the presence of DNA strand breaks, due to both acute and chronic exposure, and the micronucleus (MN) test, which is a measure of clastogenic and aneugenic events. Furthermore, since the individual response to the exogenous insults may be genetically determined, we studied the possible influence of single nucleotide polymorphism in XRCC1 and XRCC3 DNA repair genes on induced genetic damage. We also considered the effects of confounding factors like smoking, age and gender. The results indicated that the exposed subjects had significantly high levels of genetic damage. Age and gender were associated with increased values in MN, both in control and in exposed groups; the smoking habit affects MN frequency in controls, but not in workers. Furthermore we found that exposed subjects bearing at least one XRCC1 variant allele (399Gln) show higher values of MN. The present data provide the evidence to show that occupational exposure to antineoplastic drugs, even if in safety controlled conditions, represents a serious health risk. Furthermore we have shown that the presence of XRCC1 genetic polymorphism could contribute to increase the genetic damage in susceptible individuals who are occupationally exposed to dangerous substances.     

Association between urinary indicators of renal dysfunction and metal concentrations in workers chronically co-exposed to cadmium,zinc and lead

The study was carried out in 31 workers co-exposed to cadmium, lead and zinc fumes and dusts in a zinc ore refinery. Urinary cadmium, lead, zinc, β₂-M levels and NAG activities were determined to evaluate the possible dose-effect relationship between these parameters. A correlation was found between urinary cadmium, lead and zinc concentrations, and urinary β₂-M levels and NAG activities of the exposed group. A statistically significant increase was also observed for urinary NAG activity in exposed workers who had urinary cadmium concentrations > 2 μg g^?1 creatinine. However, in the same exposed group, the increment of β₂-M was not statistically significant. In conclusion, the present study thus confirms the earlier observations and may suggest the notion that the urinary NAG seems to be a more sensitive indicator than urinary β₂-M level in early stages of renal injury of moderately cadmium co-exposure with lead and zinc even at urinary cadmium concentration as low as 2 μg g^?1 creatinine. When the earlier studies on the irreversibility of cadmium-induced tubular dysfunction and the present results were taken into consideration, the present health-based biological limit proposed by the WHO (5 μg g^?1 creatinine) seems to be high for the occupational exposure to cadmium.     

Biological monitoring of lead and cadmium in human hair and nail and their correlations with biopsy materials, age and exposure

Hair and fingernails of exposed and unexposed subjects were analyzed for their lead (Pb) and cadmium (Cd) contents by atomic absorption spectrophotometer with graphite furnace and air-acetylene flame. Hair and nail Pb concentrations in occupationally exposed subjects ranged between 1.020-409.726 and 8.130-765.306 microg/g and in environmentally unexposed subjects 0.123-25.160 and 1.076-65.613 microg/g, respectively. Similarly, hair and nail Cd concentrations in occupationally exposed subjects ranged between 0.014-22.086 and 0.214-35.714 microg/g and in environmentally unexposed subjects 0.113-1.627 and 0.028-8.108 microg/g, respectively. A significant correlation was observed between Pb hair and nail concentrations in exposed subjects at P < 0.05, as compared to unexposed subjects and Cd hair and nail in exposed, as well as unexposed subjects. With respect to exposure, levels of Pb in hair and nails were found to be significant in exposed subjects, compared to unexposed ones and levels of Cd were significant only in nails of exposed ones. With respect to age, no significant correlation was found between hair and nail Pb and Cd concentrations in both exposed and unexposed subjects.     

Evaluation of cellular and humoral immunity in men after occupational exposure]

Hundred twenty seven adult men have been examined to determine an effect of the occupational exposure to lead on the immunity. A group of 77 men occupationally exposed to lead absorbed by respiratory has been selected on the basis of the determination of exposure to lead in their working places, detection of lead deposits and its metabolites in the body. Fifty men constituted a control group. They were exposed to lead corresponding to an exposure of general population. Immunological studies have shown that high lead levels in the occupational environment produced significant disorders in all stages of both types of immunological response--a decrease in the cellular and humoral immunity.     

Plasma microRNA expression and immunoregulatory cytokines in an Indian population occupationally exposed to cadmium

Following its accumulation in the body, cadmium (Cd) exposure is associated with devastating effects on multiple organ system of the human body. The immune system is one of the sensitive targets for Cd-induced toxicity. Recently, studies have demonstrated a significant role of Cd in inducing epigenetic alterations. With this background, the present study was planned to study the changes in candidate microRNA (miRNA) expression associated with immune regulation in occupationally Cd-exposed workers. One hundred individuals involved in welding and metal handicraft manufacturing, while 80 apparently healthy subjects without any prior history of occupational exposure were recruited for the study. Blood Cd level was determined by atomic absorption spectrometry. Serum cytokine levels were measured using an enzyme-linked immunosorbent assay and serum miRNA expression of candidate miRNAs (miR-146a, miR-210, and miR-222) were determined by real-time polymerase chain reaction. The median Cd level (2.40 μg/L) in the occupationally exposed workers was significantly higher than the nonexposed subjects (0.90 μg/L). Among the cytokines, interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-α) were significantly higher while IL-2 and IL-10 were significantly lower in the exposed. The expression level of miR-146a and miR-222 were significantly different between the groups with the former showing downregulation and later showing upregulation. Correlation analysis revealed a positive and negative association of miR-222 and miR-146a with blood cadmium level, IL-17 as well as TNF-α, respectively. Furthermore, the in-silico analysis revealed a significant role of the studied miRNAs in various cellular and genetic pathways. The findings of the present study demonstrate significant involvement of Cd-induced alteration in miRNAs in varied immune regulatory changes in exposed individuals.