<Emphasis Type="Italic">XRCC1</Emphasis>,<Emphasis Type="Italic"> CYP2E1</Emphasis> and<Emphasis Type="Italic"> ALDH2</Emphasis> genetic polymorphisms and sister chromatid exchange frequency alterations amongst vinyl chloride monomer-exposed polyvinyl chloride workers

Vinyl chloride monomer (VCM) is a known human carcinogen, which may be metabolized by cytochrome P450 2E1 (CYP2E1), aldehyde dehydrogenase 2 (ALDH2), and glutathione S-transferase T1 (GSTT1). A DNA-repair gene, X-ray repair cross-complementing group 1 ( XRCC1, exon 10), may also be implicated in the process of VCM-related carcinogenesis. Thus, VCM-exposed workers with inherited susceptible metabolic and DNA-repair genotypes may experience an increased risk of genotoxiciy. This study was designed to investigate whether metabolic and DNA-repair genotypes affected sister chromatid exchange (SCE) frequency in occupationally VCM-exposed workers from polyvinyl chloride (PVC) manufacturing plants. Study subjects comprised 61 male workers having experienced VCM exposure, and 29 male controls. Questionnaires were administered to obtain detailed histories of cigarette-smoking habits, alcohol consumption behavior, and occupation. The frequency of SCE in peripheral lymphocytes was determined using a standardized method, and genotypes of CYP2E1, ALDH2, GSTT1 and XRCC1 were identified by the polymerase chain reaction (PCR) procedure. Our results demonstrated that smoking, age and VCM exposure and XRCC1 ( P=0.03), CYP2E1 ( P=0.04), and ALDH2 ( P=0.08) were significantly associated with an increased SCE frequency. Further analysis of gene combinations, including CYP2E1, ALDH2 and XRCC1, revealed an increased trend for these genotypes to influence SCE frequencies for the low VCM-exposure group ( P<0.01), but not so for the high VCM-exposure group ( P=0.29) or for controls ( P=0.49). These results suggest that workers with susceptible metabolic and DNA-repair genotypes, may experience an increased risk of DNA damage elicited by VCM exposure.     

Higher urinary 1-hydroxypyrene concentration is associated with cooking practice in a Chinese population

Urinary 1-hydroxypyrene (1-OHP) is a biomarker of polycyclic aromatic hydrocarbons (PAHs) exposure. We examined urinary 1-OHP concentrations in 328 non-occupational exposed health subjects (108 females and 220 males). Each subject was questionnaired for the information of cigarette smoking and the habit of cooking practice including the cooking frequency in the kitchen (times per week), range hood opened for cooking, and fuel used for cooking. Concentrations of urinary 1-OHP (geometric mean, mumol/mol creatinine) were significantly higher in females than in males (0.50 versus 0.34, P<0.001). Cooking frequency in the kitchen had significant influence on the urinary 1-OHP concentrations in females. In females who did cooking practice in the kitchen, the urinary 1-OHP excretions were significantly higher in those who did not install the range hood compared to those who always opened the hood when cooking (0.75 versus 0.42, P=0.020). In males, cooking frequency in the kitchen and cigarette smoking were interacted on urinary 1-OHP levels. Those results imply that it is necessary for females with higher frequency of cooking and males with heavy smoking habits to improve their cooking conditions in order to reduce the risks of getting diseases including cancer.     

Frequency of sister chromatid exchange in chrysotile-exposed workers.

Chrysotile, which is an industrial carcinogen, has been shown to induce a dose-dependent increase in the frequency of sister chromatid exchange (SCE) in vitro. Authors designed this study to examine the increase of SCEs frequency in the workers occupationally exposed to chrysotile. Heparinized whole blood samples from 45 chrysotile-exposed and 45 control volunteers were cultured for 72 h. The significant difference of SCE frequency was found between chrysotile-exposed workers and control group. The highest SCEs frequency was found in chrysotile-exposed smokers, and the lowest in control non-smokers. The effect of chrysotile exposure on SCEs was marginally significant after controlling the effects of age and smoking by multiple regression analysis.     

Chromosome damage in workers in cigarette manufacturing industry

To investigate whether occupational exposure to tobacco dust is genotoxic, a group of employees in a tobacco factory was tested for structural chromosome aberrations (CA), cytokinesis-block micronucleus assay (CBMN) and sister chromatid exchanges (SCE) that are well established as indicators of early biological effects. The study group consisted of 40 tobacco workers and an equal number of matched controls. The results obtained in the exposed group showed a significant increase in chromosome aberrations (R=0.26), micronucleus frequency (R=0.56) and in sister chromatid exchanges (R=0.75), which was additionally influenced by smoking. A significant increase in high frequency cells (HFC) in the exposed group was also observed. Like the SCE frequency, the HFC frequency increased significantly in smokers of the control and exposed smokers. The study indicates that occupational exposure to tobacco dust induces genome damage. A higher risk was observed in women. The micronucleus frequency and sister chromatid exchange tests seem to be more reliable indicators of genome damage than chromosome aberrations in monitoring chronically exposed subjects.     

Study on the oxidative stress status among cement plant workers

The cement industry is considered as a major pollution problem because of dust and particulate matter emitted at various steps of cement production. In the present study, volunteer male workers from a cement factory were studied for oxidative and nitrosative stress biomarkers in relation to their serum levels of aluminum (Al) and chromium (Cr). The subjects were divided into two groups of direct and indirect exposure. Subject who worked in production steps were considered as direct exposure group, and those who worked in administration building were considered as indirect exposure group. For comparison, healthy subjects at the same age and socioeconomic status were tested as a control group. Serum levels of lipid peroxidation (LP), total antioxidant capacity (TAC), total thiol molecules (TTM), and nitric oxide (NO) as well as Al and Cr were measured. The results indicated a significant increase in Al (P = 0.001) and Cr (P = 0.009) levels in direct-exposed workers in comparison to healthy control group. Further, a significant increase in Al (P = 0.002) and Cr (P = 0.009) levels was observed in direct-exposed workers as compared to indirect-exposed one. Serum levels of TTM and TAC were significantly lower in both direct- and indirect-exposed groups in comparison to healthy control group (P = 0.00). Serum TTM and TAC were significantly lower in direct-exposed workers as compared to indirect-exposed ones (P = 0.00 and P = 0.024, respectively). There was no significant difference on the level of LP and NO among groups. A correlation was found between serum level of Cr, TAC, and platelets between direct- and indirect-exposed groups (P < 0.05). Further correlation was found among serum level of Cr and those of TTM, platelets, and chronic disease (P < 0.05). Chronic disease had a significant influence adjusted to other predictor variables on the post-shift values of Al (P < 0.05). Although plasma levels of Al and Cr were found in normal ranges, analyses confirm their role in impairment of TMM and TAC.     

The association between frequencies of mitomycin C-induced sister chromatid exchange and cancer risk in arseniasis

In order to examine whether biomarkers of cytogenetic damage and susceptibility, such as spontaneous and mitomycin C-induced sister chromatid exchange (SCE) can predict cancer development, a nested case-control study was performed in a blackfoot endemic area with known high cancer risk. A cohort of 686 residents was recruited from three villages in the arseniasis area. Personal characteristics were collected and venous blood was drawn for lymphocyte culture and stored in a refrigerator. The vital status and cancer development was followed using the National Death Registry, Cancer Registry, and Blackfoot Disease Registry. The follow up period was from August 1991 to July 1997. During this 6-year-period, 55 residents developed various types of cancer. Blood culture samples from 23 of these subjects were unsuitable for spontaneous SCE experiments and 45 of these subjects were unsuitable for mitomycin C-induced SCE experiments due to improper storage. Finally, a total of 32 cancer cases had cytogenetic samples that could be analyzed. About 32 control subjects were selected from those who did not develop cancer in the study period and these subjects were matched to cases by sex, age, smoking habits, and residential area. The results showed that there was no significant difference in the frequencies of spontaneous and mitomycin C-induced SCE between the case and control groups. There was also no significant difference in the net difference of spontaneous and mitomycin C-induced SCE between the case and control groups. These results suggest that SCEs, either spontaneous or mitomycin C-induced, might not be good markers to predict cancer risk.     

Examination of urinary mercury levels in dentists in Turkey

Mercury (Hg) is a naturally occurring element and its toxicity, especially in certain forms, has been known for many years. Exposure to Hg can occur in occupational and environmental settings. The toxicity of Hg compounds in dentistry has been an issue of increasing concern. Dental personnel are occupationally exposed to Hg vapor in their working environment and this exposure constitutes a potential risk to people in the dental surgery, mainly from the inhalation of Hg vapor and fine particles of amalgam. In this study, the urinary Hg excretion levels of 20 dentists and nine control subjects, matched for age, were determined by cold-vapor atomic absorption spectrometer (CV-AAS). The levels of Hg in the urine samples of the dentists was about three times higher than the control subjects (6.2 +/- 3.5 and 1.97 +/- 0.9 microg/L, respectively) (P <0.001). Some 90% of dentists wore both gloves and masks. Standards of hygiene (use of mask, glove and gown) may contribute to the degree of exposure. Attention to important hygiene measures, such as the avoidance of spills of Hg, cleaning of floors after such spills, ventilation and the installation of ventilation, depending on technology, should be taken into consideration. Age and smoking habits did not influence the urinary Hg excretion. Our results showed that dentists had significant exposure to Hg vapor compared to control subjects and therefore might be subject to possible adverse effects due to Hg toxicity.     

Mercury exposure monitoring for Korean schoolchildren: I. Influence of socioeconomic and demographic variables

The objective of this study was to determine the total Hg in both urine and blood samples and to investigate an association between Hg levels, and the socioeconomic and demographic factors (covariates) from school children of 7–13 years old (n=2,000) during 2005–2006. This paper was the first part of the twopart series. Part 1 introduced the effect of the factors in Hg level. The second part focused upon dietary habits, fish consumption (sources and frequency), smoking habits, alcohol consumption, residential location and other factors. The parameters in this study included parental age, income, parental educational level, and parental age at delivery. Average Hg levels in blood and urinary from both female and male subjects were 2.42±1.02 μg/L [Unit] (N=1,974) and 2.53±1.88 (N=1,528) μg/g-ct (corrected for creatinine), respectively. Moreover, total Hg levels in blood did not exceed guidelines of U. S. Environmental Protection Agency (USEPA) or the Commission of Human Biological monitoring (CHBM). Conclusively, statistical significance was elucidated between age of children and mercury levels in urine or blood. Levels of parental education also exerted a direct influence on Hg levels.     

The effect of age, sex, smoking habit and hair color on the composition of hair

Hair samples (N=83) were collected between the years 1996 and 2003 from inhabitants of Wroc?aw, a city located in Lower Silesia, south-western Poland (urbanized and industrialized region). The concentrations of 33 elements: Ca, Mg, Na, K, Cu, Zn, P, Fe, Mn, Cr, Se, B, Co, Mo, Si, V, Ni, Be, Hg, Cd, Al, Pb, As, Ba, Au, Pt, Ag, Sr, Sn, Ti, W, Sb and Zr in hair were determined by inductively coupled plasma-mass spectrometry (ICP-MS) and inductively coupled plasma-atomic emission spectrometry (ICP-AES) techniques. The effect of age, sex, smoking habits and hair color on the elemental composition of hair was investigated. Also, the obtained results were compared with literature data. It was found that the composition of hair varied with age, sex, hair color and smoking habits. This concerned the majority of elements except Ti, Se, Mn, Ni, Hg, Cd, As, Co (in the case of effect of age), Al, Cd, Co (sex), Cd, K, Ag, Ca, Co, Be (smoking habit), P, Fe, Al, Mn and Cr (hair color). Therefore, reference values for the level of the remaining elements should be normalized according to age, sex, smoking habit and hair color. This would make hair analysis more reliable.     

Urinary bladder cancer risk in relation to a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor-binding protein-3 (IGFBP3) gene

Currently, twelve validated genetic variants have been identified that are associated with urinary bladder cancer (UBC) risk. However, those validated variants explain only 5-10% of the overall inherited risk. In addition, there are more than 100 published polymorphisms still awaiting validation or disproval. A particularly promising of the latter unconfirmed polymorphisms is rs2854744 that recently has been published to be associated with UBC risk. The [A] allele of rs2854744 has been reported to be associated with a higher promoter activity of the insulin-like growth factor-binding protein-3 (IGFBP3) gene, which may lead to increased IGFBP-3 plasma levels and cancer risk. Therefore, we investigated the association of rs2854744 with UBC in the IfADo case-control series consisting of 1,450 cases and 1,725 controls from Germany, Hungary, Venezuela and Pakistan. No significant association of rs2854744 with UBC risk was obtained (all study groups combined: unadjusted P?=?0.4446; adjusted for age, gender and smoking habits P?=?0.6510), besides a small effect of the [A] allele in the Pakistani study group opposed to the original findings (unadjusted P?=?0.0508, odds ratio (OR)?=?1.43 for the multiplicative model) that diminished after adjustment for age, gender and smoking habits (P?=?0.7871; OR?=?0.93). Associations of rs2854744 with occupational exposure to urinary bladder carcinogens and smoking habits were also not present. A meta-analysis of all available case-control series including the original discovery study resulted in an OR of 1.00 (P?=?0.9562). In conclusion, we could not confirm the recently published hypothesis that rs2854744 in the IGFBP3 gene is associated with UBC risk.     

Bupropion for pharmacologic relapse prevention to smoking: predictors of outcome

The aim of this study was to identify predictors of successful relapse prevention in smokers receiving long-term sustained-release bupropion. Smokers (N= 784) who were interested in stopping smoking were enrolled in a 7-week, open-label bupropion phase. Abstinent subjects at the end of treatment and eligible to proceed (N= 429) were randomized to active bupropion or placebo through Week 52 and then followed for an additional year. The best overall predictor of less relapse to smoking was assignment to active bupropion. In aggregate, the results indicate that bupropion can be prescribed to diverse populations of smokers with expected comparable results. There was a medication effect that was independent of any predictor except older age and those who gained no or minimal weight during the open-label phase. Predictors of successful relapse prevention included lower baseline smoking rates, a Fagerstr?m Tolerance Questionnaire score of < 6, and initiation of smoking at an older age. These data should encourage others to perform similar pharmacologic relapse prevention studies with this or other pharmacotherapies.     

Study of urinary 6β-hydroxycortisol/cortisol ratio in spot urine sample as a biomarker of 3A4 enzyme activity in healthy and epileptic subjects of Egyptian population

The ratio of urinary 6 beta-hydroxycortisol/cortisol (6 beta-OHC/FC) in morning spot urine samples collected from 8:00 a.m. to 12:00 p.m. was studied using ELIZA kits (Stabiligen) in a group of healthy adult Egyptians (control group) of both sex (n=65, age range: 16-48 years). The frequency distribution of urinary 6 beta-OHC/FC ratio was widely distributed among subjects with higher values in males in comparison to females. No bimodality in either sex was observed. Another group of adult epileptic patients (n=16) was studied for the influence of chronic carbamazepine antiepileptic drug administration on urinary 6 beta-OHC/FC ratio in spot urine samples. The induction property of carbamazepine on CYP3A4 was observed through significant increase (p=0.01) in 6 beta-OHC/FC ratio among epileptic patients in comparison with control subjects. In conclusion, the frequency distribution of urinary 6 beta-OHC/FC ratio among Egyptians shows sexual dimorphism. Also, measurement of urinary 6 beta-OHC/FC ratio provides a simple non-invasive method to monitor CYP3A4 enzyme induction during administration of carbamazepine antiepileptic drug.     

Investigations on the effect of repeated hair dyeing on sister chromatid exchanges

The numbers of sister chromatid exchanges (SCE) were determined in the lymphocytes of ten volunteers (males and females) whose hair was dyed 13 times at intervals of 3–5 wk. Each volunteer used throughout the study a single commercial preparation containing a mixture of aminotoluenes, aminophenols and hydroxybenzenes, and in some cases naphthol, as the active ingredients. The findings were compared with those in a control group matched for age and sex. SCE were determined in blood samples taken before the first exposure, after a sham dyeing and after the first three and the last three actual dyeing procedures. Volunteers were carefully screened for disease, for use of medicines and for radiation exposure. Consumption of alcohol was the same in both groups, but there were more smokers in the treated group. No evidence was found of any effect of repeated hair dyeing on the frequency of SCE. In both the controls and in the hair-dyed subjects a slight decrease in SCE was detected during the course of the experiment; this was independent of sex as well as of the dyeing procedure.     

Induction of micronuclei on Greek hairdressers occupationally exposed to chemical mixtures

Since the early 20th century, hairdressers (HD) have been exposed to a wide range of harmful chemical products. To determine the possible genetic damage to HD, as a result of their occupational exposure to combinations of different chemical factors, we applied the micronucleus assay on their peripheral blood lymphocytes cultures. The micronucleus assay was performed on blood samples from 20 Greek female HD and 20 control women, having no connection with the occupation, from the same area. In the results analysis, parameters included were age, smoking habits, and duration of occupational exposure. The results of our study showed a significant increase in HD micronuclei (MN) frequency, compared to the controls (13.4 ± 1.00 vs. 8.05 ± 0.65). The frequency of large‐size MN was significantly higher in the HD and presented potential correlation with the phenomenon of aneuploidy. A statistically significant difference in the frequency of MN between HD and controls who smoked was observed, while this was not the case with the non smoker groups. However, multiple regression analysis showed no significant correlation between smoking habits and MN frequency. The observed increase of the frequency of MN in HD is attributed to the long‐term occupational exposure of HD in combination with different chemical factors. Since in the literature there are very few similar studies, further combined studies are suggested on a larger number of HD from different countries, combining biological and molecular techniques, as well as chemical analytical methods of determining and tracing the chemical factors in both the occupational environment and their organisms. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2010.     

Lack of genotoxic effect in workers exposed to very low doses of 1,3-butadiene

1,3-butadiene (BD), a probable carcinogen to humans, has been shown to have an ill-defined genotoxicity in occupationally exposed workers. In the present study, the influence of exposure to very low doses of BD and to cigarette smoking was investigated on some cytogenetic endpoints, namely, sister chromatid exchanges (SCE), chromosomal aberrations (CA) and cells with a high frequency of SCE (HFC), in peripheral blood lymphocytes. Twenty-seven male workers employed in a petrochemical plant and 26 matched controls were included in the study. As regards the airborne BD values, there was a significant difference between exposed (median BD value 1.5, min–max 0.2–69.0 μg/m³) and non-exposed workers (median BD value 0.4, min–max <0.1–3.8 μg/m³). Genotoxic biomarkers were not able to distinguish between the two groups. The frequency of SCE was higher in smokers than in non-smokers (p=0.001), with a positive correlation between the number of cigarettes smoked per day and both SCE (r=0.4; p=0.004) and HFC frequency (r=0.3; p=0.04). Multiple regression analysis confirmed the influence of cigarette smoking on the level of SCE and HFC, while these parameters were not affected by personal exposure to BD. Overall, the biomarkers of genotoxic effect investigated in our study were not able to discriminate between workers with a very low exposure to BD and controls, while it was possible to distinguish between smokers and non-smokers on the basis of SCE.Piero Lovreglio and Nenad Bukvic have contributed equally to this study     

Evaluation of urinary 8-hydroxydeoxyguanine in healthy Japanese people

The urinary concentration of 8-hydroxydeoxyguanine (8-OHdG), which is a biomarker of oxidative DNA damage, was measured in 248 healthy Japanese, and its correlations with life style, urinary metal elements, serum antioxidants, and other plasma or serum factors were investigated. The mean urinary concentration of 8-OHdG was 15.2+/-5.71 ng/mg creatinine. Mean urinary 8-OHdG was not significantly different in terms of age (<45, >or=45), gender, smoking (no, <20, >or=20), and alcohol consumption (no, occasionally, sometimes and usually). Moreover, multiple regression analysis showed a significant association between urinary 8-OHdG and urinary arsenic (As) or chromium (Cr), and a tendency for association between the former and aluminum (Al) and nickel (Ni). Age, gender and plasma or serum factors including antioxidants, lipid peroxide, HbA1c, BUN, and iron did not show such an association. The present study suggests that natural exposure to toxic metal elements such as As, Cr, and Ni may influence oxidative DNA damage in healthy people under usual environmental management. Therefore, the measurement of urinary metals such as As, Ni and Cr is prerequisite for the study of the relationship between urinary 8-OHdG and other variable factors.     

Iron status in manganese alloy production workers

The aim of this study was to investigate markers of iron status in production workers with current and long-term exposure to manganese (Mn) alloys. A total of 100 Mn-exposed male workers were compared with 100 male controls matched for age in a cross-sectional study. The geometric mean urinary Mn concentration in the exposed workers was 0.9 nmol mmol(-1) creatinine (range = 0.1-126.3), compared with 0.4 nmol mmol(-1) creatinine (range = 0.1-13.1) in the controls. The index group had been exposed to Mn for 20 years on average (range = 2.1-41.0). The geometric mean concentration of soluble transferrin receptor was lower in the exposed subjects than in the controls (2.2 vs 2.6 mg l(-1); P < 0.001) and the concentration was negatively associated with current exposure to "soluble" Mn in the inhalable aerosol fraction and with current smoking habits. An association was found between the concentration of serum soluble transferrin receptor and the concentration of Mn in whole blood (Pearson's r = 0.48; P < 0.001) in the controls. The results suggest that Mn-exposed workers have higher intracellular iron concentration in the erythrocyte precursors than the controls, resulting in a down-regulation of transferrin receptors on the surface of these cells. The concentrations of Mn in the blood of occupationally non-exposed individuals appear to be influenced by iron status, even at physiological iron levels.     

Modulation of urinary polycyclic aromatic hydrocarbon metabolites by enzyme polymorphisms in workers of the German Human Bitumen Study

Data concerning the influence of sequence variants of metabolizing enzymes on the effect modulation of current exposure to vapors and aerosols of bitumen in humans are limited. To assess the influence of 18 single-nucleotide polymorphisms (SNP) in genes coding for enzymes involved in polycyclic aromatic hydrocarbon (PAH) and amine metabolism regarding their impact on urinary markers 1-hydroxpyrene (1-OHP) and the sum of 1-, 2+9-, 3-, 4-hydroxyphenanthrene (OHPHE). Based on personal ambient monitoring data for bitumen emissions, 218 German workers exposed to vapors and aerosols of bitumen during a shift and 96 German roadside construction workers without exposure to bitumen but with similar working tasks were studied. SNP determination based on DNA aliquots isolated from blood samples by real-time PCR or direct sequencing. The impact of sequence variants on the urinary levels of 1-OHP and sum of OHPHE was estimated with mixed linear models, adjusted for age, creatinine, exposure, smoking, SNP, and time of measurement. In the mixed linear model, an increasing metabolite level of OHPHE was only slightly modulated by the CC variant of the cytochrome P450 SNP CYP1A1 3801T>C (rs4646903; P = 0.051). In contrast, GSTM1 carriers showed a significant (P= 0.046) and double-mutated variants of three NAT2-specific SNP (NAT2*341CC, P = 0.06; NAT2*481TT, P = 0.06; NAT2*803GG, P = 0.042) displayed a decreasing influence on OHPHE levels. None of the SNP studied showed a significant effect on 1-OHP. The modulating SNP effects on OHPHE in the adjusted model were less pronounced when compared with the effects observed in a recent study with 170 workers occupationally exposed to PAH in German industries. This may be due to the much lower PAH exposure in the Human Bitumen Study.     

Postlabeling analysis of polycyclic aromatic hydrocarbon-DNA adducts in white blood cells of foundry workers

Blood samples were obtained from 61 volunteers working in a Finnish iron foundry who were exposed to carcinogenic polycyclic aromatic hydrocarbons and from 19 control subjects not known to be exposed to these chemicals. Foundry workers were categorized into high, medium, or low exposure groups, based on their exposure levels to airborne benzo[a]pyrene (BaP) (high greater than 0.2, medium 0.05-0.2, low less than 0.05 micrograms BaP/m3 air). Aromatic adducts were determined in white blood cell DNA from exposed and unexposed subjects using 32P-postlabeling. There was a highly significant correlation between the estimated exposure and adduct levels as determined by analysis of variance. The levels of adducts found in the high and medium group samples ranged from 5 to over 20 adducts in 10(8) DNA nucleotides. No effects due to age, sex, or the smoking habits of the subjects were observed. Within each group, the SEM appeared rather small. This study demonstrates the utility of the 32P-postlabeling assay to assess human exposure to known and unknown environmental aromatic genotoxicants.     

Cadmium-induced nephropathy in the development of high blood pressure

In recognition of a central role of the kidney in long-term blood pressure control, we undertook an in-depth analysis of the relationship between blood pressure and kidney damage caused by environmental exposure to the common pollutants cadmium and lead. The subjects were 200 healthy Thais, 16 and 60 years of age (100 female non-smokers, 53 male non-smokers, and 47 male smokers). None of these subjects had been exposed to Cd or Pb in the workplace and their urinary Cd concentrations ranged from 0.4 to 37 nM, whereas their urinary Pb concentrations ranged from 0.1 to 30 nM. The prevalence of high blood pressure was 2%, 8% and 19%, respectively in subjects with low, average and high Cd-burden (linear trend chi2=6.4, P=0.01). Multiple regression analysis revealed a significant positive association between Cd-burden and blood pressure in male non-smokers (adjusted beta=0.31, P=0.02) and an inverse association between blood pressure and urinary Pb excretion rate in male smokers (adjusted beta=-0.38, P=0.005). Associations between Cd-burden and nephropathies were evidenced by increases in urinary excretion of beta2-microglobulin (P=0.02) and N-acetyl-beta-d-glucosaminidase (P=0.005) in subjects with high Cd-burden, compared with the subjects with average Cd-burden. In addition, an association between Cd-related nephropathy and high blood pressure was evidenced by a 20% increase in the prevalence of high blood pressure in people with NAG-uria (linear trend chi2=4.3, P=0.04). Our present study provides first evidence for a possible link between renal tubular damage and dysfunction caused by environmental Cd exposure and increased risk of high blood pressure.