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1.
R. Budhwar  M. Das  V. Bihari  S. Kumar 《Biomarkers》2013,18(4):252-257
The literature has a paucity of knowledge on the exposure and effect estimates of chromeplaters in India. In an exploratory endeavour on chromium (Cr) exposure risk assessment, blood and urinary Cr levels plus the DNA–protein crosslink content were analysed in peripheral blood lymphocytes of chromeplaters (n=24). A cross-sectional study design was selected. Non-chromeplaters (n=35) were taken as the matching control. The results show that levels of blood and urinary Cr were greater in chromeplaters. A significant increase in DNA–protein crosslink coefficients of peripheral blood lymphocytes and urinary Cr levels was observed. The results demonstrate higher exposure estimates in chromeplaters and reveal exposure to a biologically effective dose of the toxic metal. The study also validated the employed biomarkers for Cr exposure risk assessment.  相似文献   

2.
《Biomarkers》2013,18(2):86-93
Abstract

DNA-protein crosslinks were measured in peripheral blood lymphocytes of chrome-platers and controls from Bulgaria in order to evaluate a genotoxic effect of human exposure to carcinogenic Cr(VI) compounds. Chrome-platers and most of the unexposed controls were from the industrial city of Jambol; some additional controls were recruited from the seaside town of Burgas. The chrome-platers had significantly elevated levels of chromium in pre- and post-shift urine, erythrocytes and lymphocytes compared with the control subjects. The largest differences between the two groups were found in erythrocyte chromium concentrations which are considered to be indicative of Cr(VI) exposure. Despite the significant differences in internal chromium doses, levels of DNA-protein crosslinks were not significantly different between the combined controls and exposed workers. Individual DNA-protein crosslinks, however, correlated strongly with chromium in erythrocytes at low and moderate doses but at high exposures, such as among the majority of chrome-platers, these DNA adducts were saturated at maximum levels. The saturation of DNA-protein crosslinks seems to occur at 7–8 μg I-1 chromium in erythrocytes whereas a mean erythrocyte chromium among the chrome platers was as high as 22.8 μg l?1. Occupationally unexposed subjects exhibited a significant variability with respect to the erythrocyte chromium concentration, however erythrocyte chromium levels correlated closely with DNA-protein crosslinks in lymphocytes. The controls from Jambol had higher chromium concentrations in erythrocytes and elevated levels of DNA-protein crosslinks compared with Burgas controls. Occupational exposure to formaldehyde among furniture factory workers did not change levels of DNA-protein crosslinks in peripheral lymphocytes. DNA-protein crosslink measurements showed a low intraindividual variability and their levels among both controls and exposed indivduals were not affected by smoking, age or weight.  相似文献   

3.
It has been known for a number of years that chromium-containing mine slags were used as landfill in residential areas of Hudson County, New Jersey. Since one of the major lesions induced in intact cells by chromate is the DNA-Protein crosslink, we have used this lesion as a biomarker of biological effect of chromium (Cr) exposure. We have previously developed a sensitive and easy-to-perform assay to detect DNA-Protein crosslinks, based on the selective K SDS precipitation of DNA associated with protein. We examined the levels of DNA-Protein crosslinks in peripheral blood mononuclear cells of 33 individuals determined to be at risk for chromium exposure by virtue of their residence in Hudson County and their urinary Cr levels. These data were compared to the levels of DNA-Protein crosslinks among 49 controls who resided in noncontaminated areas. A complete clinical examination and urine analysis did not show any Cr-related abnormalities among the exposed population. The mean DNA-Protein crosslink level in the lymphocytes of the exposed group was 1.3±0.5% (SD), whereas the unexposed group had 0.8±0.4% (p<0.001), after adjustment for age, gender, race, smoking, and weight. Further studies in this population are needed to confirm the possible association between the high levels of DNA-Protein crosslink and Cr exposure.  相似文献   

4.
Methods are needed to assess exposure to genotoxins in humans and to improve understanding of dietary cancer prevention. The Comet assay was used to detect smoking-related exposures and dietary modulations in target tissues. Buccal scrapings, blood and faeces were collected from 38 healthy male volunteers (smokers and non-smokers) during a dietary intervention study with bread supplemented with prebiotics±antioxidants. GSTM1-genotype was determined with PCR. Buccal and peripheral lymphocytes were analysed for DNA damage using the Comet assay. Genotoxicity of faecal water (FW) was assayed in human colon HT29 clone 19A cells. 'Tail intensity' (TI) was used as a quantitative indicator of DNA damage in the Comet assay. Intervention with bread reduced DNA damage in lymphocytes of smokers (8.3±1.7% TI versus 10.2±4.1% TI, n=19), but not of non-smokers (8.6±2.8% TI versus 8.3±2.7% TI, n=15). Faecal water genotoxicity was reduced only in non-smokers (9.4±2.9% TI versus 18.9±13.1% TI, n=15) but not in smokers (15.5±10.7% TI versus 20.4±14.1% TI, n=13). The Comet assay was efficient in the detection of both smoking-related exposure (buccal cells) and efficacy of dietary intervention (faecal samples). Smokers and non-smokers profited differently from the intervention with prebiotic bread±antioxidants. Stratification of data by genotype enhanced specificity/sensitivity of the intervention effects and contributed important information on the role of susceptibility.  相似文献   

5.
Chronic exposure to n-hexane may result in peripheral neuropathy. 2,5-Hexanedione (2,5-HD) has been identified as a toxic metabolite of n-hexane. The CYP2E1, CYP1A1 and GST genes are involved in the formation of 2,5-hexanedione from n-hexane as well as the elimination of 2,5-HD-formed electrophile, and these genes are highly polymorphic in the general population. A nested case-control study in an industrial cohort was conducted to evaluate the associations between polymorphisms in these metabolic genes and n-hexane-induced peripheral nerve damage. The study subjects included 22 cases, who worked in a printing factory with symptoms of peripheral nerve damage, and 163 controls, who came from the same factory of cases. DNA was extracted from blood samples and genotyping was conducted for CYP2E1 Pst, CYP2E1 Dra, CYP2E1 Ins96, CYP1A1 Msp, GSTT1 null, GSTM1 null and GSTP1 105V. Unconditional logistic regression was applied to estimate the odds ratio and 95% confidence intervals. There were no significant differences between the two groups regarding age, sex, smoking and alcohol status. A significant association between Dra polymorphism and peripheral nerve damage was found. The frequency of CYP2E1 Dra homozygous mutation in the case group (18.2%) was higher than that in the control group (3.7%, p=0.015). Individuals with homozygote genotype (CC) of CYP2E1 Dra had a significantly higher risk of peripheral nerve damage compared with those with DD genotype (adjusted OR = 5.58, 95% CI = 1.32-23.65) after n-hexane exposure duration, sex, age, smoking and alcohol status were adjusted. No significant association was found that CYP2E1 Pst, CYP2E1 Ins96, CYP1A1 Msp, GSTT1, GSTM1, GSTP gene polymorphisms associated with the susceptibility of peripheral nerve damage. These findings suggested that CYP2E1 gene might increase the susceptibility to n-hexane-induced peripheral damage.  相似文献   

6.
Zhang M  Chen Z  Chen Q  Zou H  Lou J  He J 《Mutation research》2008,654(1):45-51
DNA damage of peripheral lymphocytes in 60 workers occupationally exposed to trivalent chromium [Cr(III)] in a tannery was studied using comet assay. The urinary and blood chromium levels were detected as a biomarker of internal exposure. The 90 subjects were divided into three groups: (i) exposure group I included 30 tannery workers highly exposed to chromium from tanning department; (ii) exposure group II included 30 tannery workers with moderate chromium exposure from finishing department; (iii) control group included 30 individuals without exposure to physical or chemical genotoxic agents. No significant difference was found among the three groups for age and smoking. The results showed that the medians of blood and urinary Cr of two exposure groups were significantly higher than those of control group (P<0.01). And the medians of blood and urinary Cr of exposure group I were significantly higher than those of exposure group II (P<0.05 or P<0.01). The medians of mean tail length (MTL) of the three groups were 5.33 (2.90-8.50), 3.43 (2.31-8.29) and 2.04 (0.09-3.83) microm, respectively; The medians of mean tail moment (MTM) of the three groups were 6.28 (2.14-11.81), 3.41 (1.25-11.07) and 0.53 (0.13-3.29), respectively. The MTL and MTM of two exposure groups were significantly higher than those of control group (P<0.01). The MTL and MTM of exposure group I were significantly higher than those of exposure group II (P<0.01). The results of the present investigation suggest that occupational exposure to trivalent chromium can lead to a detectable DNA damage of human peripheral lymphocytes. Moreover, DNA damage was associated with chromium levels in blood. DNA damage may serve as a valuable effective biomarker and total chromium in blood may serve as a useful internal exposure biomarker in the population occupationally exposed to trivalent chromium.  相似文献   

7.
Current evidence suggests that the neurotoxic effects of lead may partially be mediated through interference with the dopaminergic system. The aim of this study was to assess the levels of two peripheral dopaminergic markers- serum prolactin (Pro-S) and urinary homovanillic acid (HVA-U) - in children living around two lead smelters, who are presumed to be exposed to high environmental lead pollution (n = 200), and compare their results with 200 age- and sex-matched controls living in an area unpolluted by heavy metals, giving a total of 400 children (200 boys and 200 girls). The influence of lead exposure on HVA-U and Pro-S was assessed by stepwise multiple regression, testing lead concentrations in blood (Pb-B), age, sex and area of residence as predictors. Though lead levels were significantly higher in boys and in the lead-polluted environment, mean Pb-B values were relatively low, indicating a low uptake of lead in the contaminated environment (39.5 µg l-1, range 4.6-165µgl-1, n = 200), and no significant correlation could be found with either Pro-S or HVA-U. However, when the subgroup of 121 children with Pb-B levels above 50 µg l-1 were considered, a weak positive correlation was found between Pb-B and HVA-U (r2 = 0.04, p = 0.03), whilst in the even smaller subgroup of 15 children with Pb-B levels above 100 µg l-1, Pro-S appeared to be positively correlated with Pb-B, though the numbers of children were too small for the correlation to reach statistical significance (p = 0.095). These weak associations, probably not important in biological terms, indicate that Pro-S and HVA-U are not useful biomarkers at present exposure levels to lead in the environment. Nevertheless, the finding of subtle biochemical alterations in the dopaminergic system at Pb-B levels of around 100µgl-1 supports the recommended setting of the action level at this value.  相似文献   

8.
Oxidative DNA damage and repair, as measured by 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine and DNA samples were studied in association with work-related diesel exhaust exposure among garage and waste collection workers. Seasonal variations of the urinary 8-OHdG levels in pre- and two post-workshift urine samples of 29 exposed workers and 36 control persons were evaluated. The mean±SE levels of post-workshift 8-OHdG (μmol/mol crea) were 1.52±0.44 in winter and 1.61±0.33 in summer for the exposed workers, and 1.56±0.61 in winter and 1.43±0.49 in summer for the controls, respectively. No significant difference in the urinary 8-OHdG levels between exposed workers and control subjects in winter (p=0.923) and summer (p=0.350) was observed. A linear mixed model, adjusted for years of employment, age, ex/non-smoking and BMI, indicated no significant dose exposure-relationships between the urinary 8-OHdG and 15 PAH air concentrations nor between the 8-OHdG and 7 PAH monohydroxy-metabolites analyzed in the same workers. 8-OHdG was also analyzed in the mononuclear cell DNA of 19 exposed and 18 control subjects. The mean value of 8-OHdG/non-modified 2'-deoxyguanosine (8-OHdG/105 dG±SE) were 4.89±0.17 for the exposed and 4.11±0.16 for the control persons, which showed no correlation with the urinary 8-OHdG levels (r=0.01, n=28, P=0.96). The PAH exposure at workplaces was mainly composed of volatile compounds, particularly naphthalene, suggesting low exposure through the respiratory tract and a low effect of PAH in ROS induction.  相似文献   

9.
DNA damage of peripheral lymphocytes in 60 workers occupationally exposed to trivalent chromium [Cr(III)] in a tannery was studied using comet assay. The urinary and blood chromium levels were detected as a biomarker of internal exposure. The 90 subjects were divided into three groups: (i) exposure group I included 30 tannery workers highly exposed to chromium from tanning department; (ii) exposure group II included 30 tannery workers with moderate chromium exposure from finishing department; (iii) control group included 30 individuals without exposure to physical or chemical genotoxic agents. No significant difference was found among the three groups for age and smoking. The results showed that the medians of blood and urinary Cr of two exposure groups were significantly higher than those of control group (P < 0.01). And the medians of blood and urinary Cr of exposure group I were significantly higher than those of exposure group II (P < 0.05 or P < 0.01). The medians of mean tail length (MTL) of the three groups were 5.33 (2.90–8.50), 3.43 (2.31–8.29) and 2.04 (0.09–3.83) μm, respectively; The medians of mean tail moment (MTM) of the three groups were 6.28 (2.14–11.81), 3.41 (1.25–11.07) and 0.53 (0.13–3.29), respectively. The MTL and MTM of two exposure groups were significantly higher than those of control group (P < 0.01). The MTL and MTM of exposure group I were significantly higher than those of exposure group II (P < 0.01). The results of the present investigation suggest that occupational exposure to trivalent chromium can lead to a detectable DNA damage of human peripheral lymphocytes. Moreover, DNA damage was associated with chromium levels in blood. DNA damage may serve as a valuable effective biomarker and total chromium in blood may serve as a useful internal exposure biomarker in the population occupationally exposed to trivalent chromium.  相似文献   

10.
In Helix pomatia L. recordings have been made of 91 single neurons from the cerebral ganglia during peripheral thermal stimulation of the lip region. Temperatures ranged between 12 and 32°C. Different reactions to thermal stimulation could be observed: hyperpolarisation (n=43), depolarisation (n=9), increasing frequency of action potentials (n=10), decreasing frequency of action potentials (n=3). A number of cells did not show any changes in neuronal activity (n=26). The assumption that distinct cell clusters are responsible for the processing of thermal stimuli had to be rejected since cells responding to peripheral thermal stimulation were found in all parts of the ganglia.  相似文献   

11.
The objective of this study was to evaluate the efficacy of combinations of PMSG treatment and ram contact on the reproductive performance of progestagen-treated ewes during three different times of the year, Febraury (early anestrus), July (late anestrus) and October (breeding season). A total of 109 multiparous Dorset ewes was used. Ewes were treated with intravaginal progestagen pessaries for 12 days, injected with 500 IU PMSG at pessary removal and either isolated from rams prior to mating (n = 12, February; n = 12, July; n = 8, October) or exposed to rams during pessary treatment (n = 17, February; n = 12, July; n = 8, October). A third treatment group (n = 18, February; n = 6, July; n = 8, October) received pessaries and ram exposure but no PMSG. An additional treatment of progestagen pessaries alone was included in October (n = 8). There were no differences among treatments in their ability to induce estrus at different times of the year, but incidence of estrus tended (P < 0.10) to be lower for PMSG treatment during the July breeding. During February, the use of pessaries with PMSG treatment increased (P < 0.05) conception and lambing rates, whereas ram contact was without any beneficial effects. The trend was reversed during July breeding, when ram contact increased (P < 0.05) fertility of progestagen-treated ewes compared with other treatment combinations. Pessaries alone were sufficient to attain acceptable levels of fertility and fecundity in October.  相似文献   

12.
Smokers are exposed to a number of carcinogenic compounds including aromatic amines such as 4-aminobiphenyl. Antioxidants are thought to be involved in the defence against the damaging effect of such carcinogens. Recently it has been shown that plasma antioxidant status in smokers is diminished compared with non-smokers. In this study we investigated in 40 smokers whether the trolox equivalent antioxidant capacity (TEAC) in plasma could be quantitatively related to exposure to cigarette smoke. The biomarkers 4-aminobiphenylhaemoglobin (4-ABP-Hb) adduct and cotinine were determined as indices of cigarette smoke exposure. A correlation between 4-ABP-Hb adduct levels and plasma cotinine levels was found for the whole population studied, who smoked 4-70 cigarettes per day (n = 40, r2 = 0.12, p = 0.03). A significant inverse relationship was found between TEAC and 4-ABP-Hb levels (n = 40, r2 = 0.17, p = 0.008). Multiple regression analysis showed a strong relationship between 4-ABP-Hb levels and plasma TEAC and cotinine levels (n = 40, r2 =0.29, p = 0.002). These findings provide strong evidence that the 4- ABP-Hb adduct represents a valuable biomarker of (internal) exposure to tobacco smoke, and also that the formation of this marker is dependent on the plasma antioxidant status. The multiple regression analysis results show that the measure of effect (4-ABP-Hb adduct formation) is largely determined by dose (cotinine) and protection (TEAC).  相似文献   

13.
A new method was developed for the analysis of DNA-protein crosslinks in Neurospora crassa. The formations of DNA-protein and DNA-DNA crosslinks were assayed following exposure of spheroplasts to HN2. Both types of crosslink were detected and were found to be repaired during recovery. Moreover a mutant sensitive to HN2 was defective in the removal of both types of crosslink.  相似文献   

14.
A method was developed for simultaneous quantification of urinary 1- and 2-naphthols, 3- and 9-phenanthrols and 1-pyrenol using gas chromatography with mass spectrometry (GC-MS). This method was applied to urine samples from coke oven workers (n =28) and controls (n =22) from Northern China. Geometric mean levels of urinary 1-naphthol (58.8 μg l-1), 2-naphthol (34.1 μg l-1), 3-phenanthrol (7.35 μg l-1), 9-phenanthrol (1.28 μg l-1) and 1-pyrenol (25.4 μg l-1) were significantly higher among coke oven workers than controls. All the substances tested were highest among top-of-oven workers, who had 15-fold higher 1-naphthol, eight-fold higher 2-naphthol and 20-fold higher 1-pyrenol levels compared with controls. Using multiple linear regression models, 72.5% of the variation in 1- and 2-naphthol and 82.8% of the variation in 1-pyrenol were explained by the concentration of naphthalene or pyrene in the urine, the work category and the smoking intensity. Cigarette consumption significantly contributed to levels of urinary 1-pyrenol and naphthols, particularly 2-naphthol. A negative relationship between work category and the ratio of naphthols/1-pyrenol was observed among smokers. Our results suggest that urinary naphthols and phenanthrols reflect polycyclic aromatic hydrocarbon (PAH) exposure as well as the widely used 1-pyrenol, and that interactions between cigarette smoking and PAH exposure result in different patterns of metabolism for individual PAHs.  相似文献   

15.
Smoking-related aromatic DNA adducts in lymphocytes were measured from smokers (n = 76), ex-smokers (n = 25) and non-smokers (n = 56) by the 32P-postlabelling method, to clarify whether a genetic polymorphism for metabolic enzymes could explain the inter-individual variation of DNA adduct levels. Adduct levels were compared with respect to smoking status and polymorphic genotypes of cytochrome P4501A1 (CYP1A1) and glutathione S-transferase M1 (GTSM1). The mean adduct level (1.24 per 108 nucleotides) in smokers was significantly higher than that (0.85 per 108) in non-smokers. Although we expected higher adduct levels in the CYP1A1 variant or GSTM1 null subjects, the adduct level in 'GSN1 nulls' was significantly lower than that in 'GSTM1 presents' among smokers. DNA adduct levels had significant positive correlations with smoking indices such as number of cigarettes or smoking years in all subjects. In smokers only, however, no correlation was found, because there were negative correlations between adduct levels and smoking dose in GSTM1 null genotypes. CYP1A1 genotypes had no effects on adduct levels.  相似文献   

16.
Heat shock protein 72 (HSP72) is the most inducible HSP, but is not always increased in lymphocytes following exercise. This field study examined whether lymphocyte HSP72 was increased in hyperthermic (Trec>39.0 °C) male athletes following a 14 km competitive race in cool conditions (ambient temperature 11.2 °C). A comparison was also made between control runners (n=7) and those treated for exertional heat illness (n=9). Lymphocyte HSP72 was not increased in control runners immediately post- compared with pre-race, and there was no difference between both groups of runners. A second study of the race (ambient temperature 14.6 °C) found that lymphocyte HSP72 in control (n=7) and treated (n=9) athletes was higher 2 days post- compared with immediately post-race (p<0.01) and these increases were correlated with post-exercise Trec (p<0.05).  相似文献   

17.
We measured transforming growth factor (TGF)-β-dependent biomarkers in plasma and in peripheral blood mononuclear cells (PBMCs) to identify suitable pharmacodynamic markers for future clinical trials with TGF-β inhibitors. Forty-nine patients with bone metastasis were enrolled in the study, including patients with breast (n=23) and prostate cancer (n=15). Plasma TGF-β1 levels were elevated in more than half of the cancer patients (geometric mean 2.63 ng ml-1) and positively correlated with increased platelet factor 4 (PF4) levels, parathyroid-related protein (PTHrP), von Willebrand Factor (vWF) and interleukin (IL)-10. PBMC were stimulated ex vivo to determine the individual biological variability of an ex vivo assay measuring pSMAD expression. This assay performed sufficiently well to allow its future use in a clinical trial of a TGF-β inhibitor.  相似文献   

18.
Background: To analyse the post-partum concentrations of intra- and extra-cellular blood antioxidants in women with uncomplicated pregnancies.

Methods: Whole blood and plasma thiols, plasma vitamin E and C, serum cholesterol and triglyceride, ferric reducing ability of plasma (FRAP) concentrations were compared between women delivered by caesarean section (n=17) or spontaneous delivery (n=10). A repeated mixed model was used for statistical analysis.

Results: The majority of whole blood thiols increased significantly in both groups the first days post-partum. However, within the caesarean group free cysteine, oxidised cysteine, homocysteine and glutathione and plasma cysteine and homocysteine levels dropped significantly after 24 h, while FRAP levels peaked significantly in this group. Plasma vitamin E levels decreased significantly in both groups within 24 to 48 h after delivery. Independent of the way of delivery whole blood and plasma thiols were significantly increased and vitamin E levels were significantly decreased 3 months post-partum while plasma vitamin C levels and FRAP were unchanged compared to ante-partum levels.

Discussion: Decreased plasma vitamin E levels shortly post-partum are associated with decreased lipid peroxidation. The 24 h post-partum drop of some plasma and whole blood thiols in the caesarean group may be due to prolonged fasting.  相似文献   

19.
An immunoassay that quantifies urinary S-phenylmercapturic acid (PMA), a benzene-specific biomarker, has been developed and its potential usefulness as a screening tool for monitoring occupational exposure to benzene has been demonstrated. Analytical reliability has been confirmed by correlation of results with gas chromatography-mass spectrometry (GC/MS) data (R = 0.92). The assay has been configured as a competitive enzyme-linked immunosorbent assay (ELISA) to facilitate rapid throughput of samples. The ELISA has a working range of 40-1200 nmol l-1 urinary PMA and appears to be unaffected by the presence of structurally related urinary metabolites. Background levels of 0-1.9µmol PMA/mol creatinine (mean 0.9 µmol mol-1, n = 32) were measured in non-smoking control subjects. Recent exposures to benzene (8 h time-weighted averages-TWA), during diverse industrial processes, over the range 0-4.8ppm were identified by application of the assay in biological monitoring programmes.  相似文献   

20.
In India, fired clay bricks are produced in small-scale factories. There are 60, 000 active brick kilns, providing employment to nearly 12 million people in different suboccupations. This industry is largely non-mechanized and operates from November to June. Almost all the workers are exposed to direct sunlight for 8-10 h a day. Cellular DNA-protein crosslinks (DPCs) are the biologically active nucleoprotein complexes formed between DNA and proteins. Ultraviolet light and gamma-rays, and other suspected carcinogens in humans, induce DPC formation in blood cells. DPCs have therefore been identified as a biomarker for monitoring exposure to these hazardous agents. Here we report steady-state levels of DPCs in human peripheral lymphocytes from 46 brick-kiln workers exposed occupationally for 8-10 h a day to solar radiation in brickfields and 25 unexposed controls. A significant increase (p <0.05) in DPC content and DPC coefficients in peripheral lymphocytes was observed in the brick-kiln workers compared with the controls. The data suggest that the DPC content of lymphocytes could be a possible biomarker of exposure to solar radiation. However, further work is necessary to confirm this.  相似文献   

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