Association of GSTM1 and GSTT1 polymorphisms with DNA damage in coal-tar workers

DNA damage was evaluated by alkaline comet assay in peripheral blood lymphocytes of 115 coal-tar workers occupationally exposed to polycyclic aromatic hydrocarbons (PAHs) and 105 control subjects. The effect of polymorphisms of glutathione S-transferase (GST) genotypes on the DNA damage was assessed. The mean tail moment (TM) value in the coal-tar workers was significantly higher as compared to the control subjects (12.06 ± 0.55 versus 0.44 ± 0.31; P < 0.05). No significant association (P > 0.05) between the GSTT1 and GSTM1 genotypes and the TM values was found, however highest mean rank TM value was reported in GSTM1 null and GSTT1 null genotypes in both control and exposed subjects. Our results suggest that there is increased DNA damage in coal-tar workers due to PAHs exposure. Polymorphisms in GSTM1 and GSTT1 genes do not show significant effect (P > 0.05) on DNA damage.     

Ethnic and genetic differences in metabolism genes and risk of toxicity and cancer.

Individual risk of toxicity or cancer can be affected by one's exposure to sufficiently high doses of particular environmental agents (or mixtures), combined with each person's underlying genetic predisposition. The development of unequivocal DNA tests for genetic susceptibility to toxicity and cancer and the identification of individuals at increased risk, would revolutionize the fields of public health and preventive medicine. A growing number of human genetic polymorphisms in drug-metabolizing enzymes (DMEs) and the receptors controlling DME expression, are being characterized, some of these have been shown to be correlated with risk of toxicity or cancer, whereas, others presently remain equivocal and require further study. 'Phase I' DMEs, many of which represent cytochromes P450, sometimes metabolically activate pro-carcinogens to genotoxic electrophilic intermediates and other times are involved in detoxification. 'Phase II' DMEs are sometimes activating, but usually they conjugate Phase I intermediates to water-soluble derivatives, to complete the detoxification cycle. Genetic differences in the regulation, expression and activity of genes coding for Phase I and Phase II DMEs and DME receptors that control DME activity levels, can be crucial factors in defining cancer susceptibility and the toxic or carcinogenic power of environmental chemicals. In this review, our current knowledge about polymorphisms in several of these genes is summarized.     

A critique of benzene exposure in the general population

Benzene risk assessment indicates that exposure to a time-weighted average (TWA) of 1-5 parts per million (ppm) benzene in ambient air for 40 years is associated with an increased risk of acute myeloid leukemia. Decreased white blood cell count, platelet count and other hematological indices have also been observed in persons exposed to as low as 1 ppm airborne benzene. Evidence from studies worldwide consistently shows elevated levels of benzene biomarkers that are equivalent to 0.1-2 ppm benzene in ambient air, or even higher in the general population without occupational exposure to benzene (including children). The public health significance of these observations depends on to what extent these levels reflect actual benzene exposure, and whether such exposures are life-long or at least occur frequently enough to pose a possible health threat. We reviewed the evidence and discussed possible explanations for these observations. It was concluded that while there is reason to suspect that benzene contributes significantly to elevated levels of biomarkers in the general population, there is growing concern that this cannot be definitively ascertained without concomitant consideration of the role of other factors such as metabolic polymorphisms and sources of biomarkers other than benzene, which have been insufficiently studied to date. Such studies are urgently needed for valid assessment of this potential public health problem.     

Indoor and outdoor personal exposure to benzene in Athens, Greece

OBJECTIVE: To evaluate the exposure of urban inhabitants to atmospheric benzene in Athens, Greece. METHODS: Fifty non-smoker volunteers from selected occupational groups and their homes were monitored by passive air samplers for six 5-day periods during a year. An activity diary was completed during each sampling period and relevant data were collected by a questionnaire at the beginning of the study. Additional data on urban levels on benzene were also available. RESULTS: Average benzene home and personal levels in six monitoring campaigns varied between 6.0-13.4 and 13.1-24.6 microg/m(3), respectively. Urban levels varied between 15.4 and 27.9 microg/m(3) with an annual mean of 20.4 microg/m(3). Wind speed seems to determine largely home levels and personal exposure. Proximity to busy road holds also an important influence on indoor benzene levels. Adjusted for seasonal or climate variation, other significant prognostic factors of personal exposure were home levels, total time spent outdoors and transportation mean. Time spent outdoors explains the strong relationship between occupation and personal levels of exposure. Wind had similar effect in clearing indoor and urban pollution in Athens; lessen personal exposure and home levels about 2-2.5 microg/m(3) per 1 m/s increase in speed. CONCLUSIONS: Factors related to climate (use of non-absorbent materials for wall and floor covering and frequent ventilation) might be one explanation for homes' high clearing rate. Our exposure pattern, which suggests that outdoors work give the greater contribution to benzene exposure of Athens citizens, is uncommon in northern towns of Europe. Policy makers have to take in account these differences in establishing guidelines for ambient benzene exposure.     

Biomonitoring of benzene and 1,3-butadiene exposure and early biological effects in traffic policemen

The objective of this study was to determine benzene and 1,3-butadiene exposure through ambient air and personal air monitoring, as well as through biomarkers of exposure, and to evaluate the potential health risk of exposure through the use of biomarkers of early biological effects in central Bangkok traffic policemen. Ambient air concentrations of benzene and 1,3-butadiene at the roadsides were significantly higher than in police offices used as control sites (p < 0.001). Traffic policemen had a significantly higher exposure to benzene (median 38.62 μg/m³) and 1,3-butadiene (median 3.08 μg/m³) than office policemen (median 6.17 μg/m³ for benzene and 0.37 μg/m³ for 1,3-butadiene) (p < 0.001). Biomarkers of benzene exposure, blood benzene, and urinary metabolite, trans, trans-muconic acid were significantly higher in traffic policemen than office policemen (p < 0.001). No significant difference between traffic and office policemen was found in urinary benzene metabolite, S-phenyl mercapturic acid, or in urinary 1,3-butadiene metabolite, monohydroxy-butenyl mercapturic acid. Biomarkers of early biological effects, 8-hydroxy-2′-deoxyguanosine in leukocytes (8-OHdG), DNA-strand breaks, and DNA-repair capacity, measured as an increase in gamma ray-induced chromosome aberrations were significantly higher in traffic policemen than controls (p < 0.001 for 8-OHdG, p < 0.01 for tail length, p < 0.001 for olive tail moment, p < 0.05 for dicentrics and p < 0.01 for deletions). Multiple regression model including individual exposure, biomarkers of exposure, ages and years of work as independent variables showed that only the levels of individual 1,3-butadiene exposure were significantly associated with 8-OHdG and olive tail moment at p < 0.0001 indicating more influence of 1,3-butadiene on DNA damage. These results indicated that traffic policemen, who are exposed to benzene and 1,3-butadiene at the roadside in central Bangkok, are potentially at a higher risk for development of diseases such as cancer than office policemen.     

Mercury exposure and oxidative stress in communities of the Brazilian Amazon

This study was designed to assess possible associations between biomarkers of mercury (Hg) exposure and oxidative stress in fish-eating Amazonian communities. Clinical samples were obtained from riparians living in the Brazilian Amazon. Biomarkers of oxidative stress (glutathione - GSH, glutathione peroxidase - GSH-Px, catalase - CAT, activity and reactivation index of δ-aminolevulinate dehydratase - ALA-D (R%) were determined in blood. Total Hg was measured in whole blood (B-Hg), plasma (P-Hg) and hair (H-Hg). Association between biomarkers of Hg exposure and oxidative stress were examined using multiple regression models, including age, gender, alcohol consumption, smoking status, fish consumption and then stratified for gender. Significant inverse relations were observed between GSH-Px, GSH, CAT, ALA-D activity and B-Hg or H-Hg (p < 0.05). ALA-D reactivation index was positively related to B-Hg (p < 0.0001). P-Hg was directly related to ALA-D reactivation index and inversely associated with GSH-Px, GSH, and ALA-D activity (p < 0.05). When stratified for gender, women showed significant inverse associations between all biomarkers of Hg exposure and CAT (p < 0.05) or GSH (p < 0.05), while for men only P-Hg showed a significant inverse relation with GSH (p < 0.001). Our results clearly demonstrated an association between Hg exposure and oxidative stress. Moreover, for B-Hg, P-Hg and H-Hg gender differences were present.     

Induction of CYP1A and DNA damage in the fathead minnow (Pimephales promelas) following exposure to biosolids

Biosolids (treated sewage sludge) are increasingly disposed of on land. Thus particle-sorbed and dissolved constituents have the potential to enter nearby watersheds. Although organic contaminants are known to be present in biosolids these are not currently regulated and little data exist on their potential toxicity to aquatic organisms. We exposed Pimephales promelas to two concentrations of biosolids (0.5 and 2.5 g l(-1)) for 28-days (static-renewal) and characterized contaminants present and the extent of CYP1A and DNA damage induction at various time points. Many organic contaminants were detected in the biosolids, with polycyclic aromatic hydrocarbons (PAHs) being the dominant class. Substantial levels of polybrominated diphenyl ethers (PBDEs) and nonylphenols (NPs) were also present. Significant induction of hepatic CYP1A protein compared with controls (P<0.05) was observed in both low (0.5 g l(-1)) and high (2.5 g l(-1)) exposed fish from Day 7. CYP1A levels peaked at Day 21 with 21-fold and 8-fold inductions over controls in high and low dose fish respectively. Induction of DNA damage in hepatocytes (single strand breaks as measured using the COMET assay) was observed in both exposures compared with controls on Days 14 and 28 (P<0.05). A significant correlation was found between CYP1A induction and DNA damage (Pearson correlation index, P<0.05). It is plausible that activation of PAHs may be responsible for the induction of CYP1A and resulting increase in DNA damage. Our data show the potential for detrimental effects in the event of exposure of aquatic organisms to biosolids and the need for further investigations of possible impacts due to constituents not covered by current guidelines.     

School attendance and daily respiratory symptoms in children: influence of moisture damage

We investigated the effect of weekends and school holidays on the daily frequency and severity of respiratory and other symptoms among children attending schools with (index) or without (reference) moisture damage in Spain, the Netherlands, and Finland. Throughout 1 year, parents of 419 children with a respiratory condition attending index (n=15) or reference (n=10) primary schools completed three symptom diaries. We assessed associations between lower respiratory tract, upper respiratory tract or allergy, and other symptom scores and school day, weekend, or summer holiday using mixed regression models stratified by country and moisture damage. We evaluated interactions between moisture damage and type of day. We combined country‐specific estimates (incidence rate ratios [IRRs] and 95% confidence interval [CI]) in meta‐analyses. Symptom scores were lower during weekends and holiday. Lower respiratory tract symptoms were statistically significantly less common during holiday with strongest effect in index schools (IRR=0.7; CI=0.6–0.8). Reporting of other symptoms was more reduced during holiday in index (IRR=0.6; CI=0.4–0.9) than in reference (IRR=0.95; CI=0.8–1.2) schools (interaction P<.01). In conclusion, symptoms were less frequent and/or severe during summer holiday and weekends. This pattern was stronger among children attending moisture‐damaged schools, suggesting potential improvement in moisture damage‐related symptoms during school breaks.     

Associations among genetic susceptibility, DNA damage, and pregnancy outcomes of expectant mothers exposed to environmental tobacco smoke

This study determined the effects of environmental tobacco smoke (ETS) on fetal growth by measuring neonatal birth outcomes and the extent of maternal DNA damage, and investigating the relationships among gene polymorphisms, genotoxicity, and pregnancy outcomes of expectant mothers who had exposed to tobacco smoke. This prospective study enrolled 685 pregnant women who completed an initial questionnaire at three central Taiwan hospitals between 2003 and 2004. Genotype analyses of CYP1A1, GSTT1, GSTM1, and NAT2 were performed from 421 women. A total of 398 women completed the follow-up analysis and successfully delivered a live single baby (n=384). Comet assay was performed for 18 smokers, 143 ETS-exposed subjects and 130 non-smokers to measure DNA damage. Analytical findings indicated that the levels of DNA damage among smokers and ETS-exposed subjects were significantly higher than that of non-smokers. DNA damage score in the ETS-exposed group was 82.5+/-41.2 and 64.1+/-39.4 for the nonsmoking group (p<0.001). Risk of DNA damage (DNA strand breakage, sister chromatid exchange, cell transformation and escalation of cytotoxicity) for subjects exposed to ETS was 4.35 times (adjusted odds ratio; 95% CI, 1.54-12.28) greater than that of non-exposed to tobacco smoke at home. Average birth weight of neonates born to subjects with extremely serious DNA damage (within the 90th percentile, DNA damage score >or =129.5) was 141 g lighter than that of those with DNA damage score <129.5 (p=0.09). The degree of DNA lesion was not related to metabolic polymorphic genes. The results of this study suggest that comet assay are reliable biomarkers for monitoring pregnant women exposed to tobacco smoke and indicate fetal growth effects from environmental exposure to tobacco smoke.     

桥梁损伤辨识中数据融合与遗传算法的应用

介绍了基本遗传算法和改进遗传算法,并在位移与频率振型基础上进行桥梁损伤识别,基于模式逻辑实现数据融合,从实例分析中,看出通过改进的遗传算法对桥梁结构进行损伤识别,比传统遗传算法有更好的识别性能,识别结果更加准确,有必要在实际桥梁损伤识别中加大利用和推广。     

Effects of nano-scale TiO2, ZnO and their bulk counterparts on zebrafish: acute toxicity, oxidative stress and oxidative damage

The acute toxicity and oxidative effects of nano-scale titanium dioxide, zinc oxide and their bulk counterparts in zebrafish were studied. It was found that although the size distribution of nanoparticles (NPs) was similar to that of the bulk particles in suspension, the acute toxicity of the TiO₂ NPs (96-h LC₅₀ of 124.5 mg/L) to zebrafish was greater than that of the bulk TiO₂, which was essentially non-toxic. The acute toxicities observed for ZnO NPs, a bulk ZnO suspension, and a Zn²⁺ solution were quite similar to each other (96-h LC₅₀ of 4.92, 3.31 and 8.06 mg/L, respectively). In order to explore the underlying toxicity mechanisms of NPs, ·OH radicals generated by NPs in suspensions and five biomarkers of oxidative effects, i.e. superoxide dismutase, catalase activities, malondialdehyde, reduced glutathione and protein carbonyl were investigated. Results showed that after the illumination for 96 h, the quantities of ·OH in the NP suspensions were much higher than ones in the bulk particles suspensions. The malondialdehyde content of zebrafish gills exposed to either illumination or dark were 217.2% and 174.3% of controls, respectively. This discrepancy indicates the occurrence of lipid peroxidation which is partly due to the generation of ·OH. In contrast, exposure to 5 mg/L ZnO NPs and bulk ZnO suspension induced oxidative stress in the gills without oxidative damage. Oxidative effects were more severe in the livers, where the protein carbonyl content, in the light and dark groups exposed to 50 mg/L TiO₂ NPs, was 178.1% and 139.7% of controls, respectively. The malondialdehyde levels in the liver of fish exposed to 5 mg/L ZnO NPs and bulk ZnO were elevated (204.2% and 286.9% of controls, respectively). Additionally, gut tissues exhibited oxidative effects after exposure to NP suspensions. These results highlight the importance of a systematic assessment of metal oxide NP toxicity mechanisms.     

Toxicity of linear alkylbenzene sulfonate in anaerobic digestion: influence of exposure time

The inhibition of anaerobic digestion by the anionic surfactant linear alkylbenzene sulfonate was studied. The development of bacterial activity during several weeks was monitored by performing batch degradation tests with acetate and propionate. In the first phase the decay of activity without surfactant addition was studied. After the addition of the surfactant an immediate inhibition was detected. Subsequently, the degradation activity continued to decrease with increasing exposure time. Both, the immediate inhibition and the rate of the subsequent decrease of activity were dependent on the surfactant concentration. A kinetic model is presented that describes this behavior. A surfactant concentration of 14 mg L(-1) causes a 50% immediate inhibition of acetate degradation (27 mg L(-1) in the case of propionate degradation). Additionally, each 12 mg L(-1) of surfactant increases the decay rate of acetate degradation activity by a factor 10 (23 mg L(-1) for propionate degradation). A deviation from this model occurs at low surfactant concentrations (<3 mg L(-1)), where a slight stimulation of bacterial activity was observed. The above-mentioned concentrations refer to measured surfactant concentrations. These were substantially lower than the nominal concentrations (added surfactant per volume). This discrepancy is explained by adsorption of the surfactant to the biomass. Finally, the importance of the presented kinetic model and the significance of surfactant toxicity for anaerobic digestion are discussed.     

Urban population exposure to lead and cadmium in east and south-east Asia

Information is still scarce for many Asian countries on general population exposure to two potentially toxic heavy metals of lead (Pb) and cadmium (Cd). The present review on publications from this study group is intended to provide an overview of the non-occupational exposure to Pb and Cd among general populations in east and south-east Asia. During the period of 1991-1998, surveys were conducted in four cities in south-east Asia, five cities in mainland China, and two cities each in Japan and Korea. Peripheral blood, morning spot urine and 24-h food duplicate samples were collected from 20-50 non-smoking adult women in each survey site. The samples were digested by heating in the presence of mineral acids, and then analyzed by inductively-coupled plasma mass spectrometry for the metals in blood (Pb-B and Cd-B), in urine (Pb-U and Cd-U), and in food duplicate (Pb-F and Cd-F). Measures were subjected to statistical analysis with an assumption of log-normal distribution. Pb-B, Pb-U and Pb-F levels varied substantially among the 11 urban sites; GM distributed in ranges of 32-65 microg/l for Pb-B, 2.1-7.5 microg/g cr (creatinine) for Pb-U, and 7-32 microg/day for Pb-F. The same was also the case for Cd exposure parameters, the distribution ranges being 0.5-1.8 microg/l for Cd-B, 1.2-3.1 microg/g cr for Cd-U, and 5-32 microg/day for Cd-F. It appeared that the exposure to Pb and Cd was highest in Kuala Lumpur, and Tokyo + Kyoto, respectively, and lowest in Tokyo + Kyoto and in Manila. Additional surveys in Japan showed that Pb exposure was even lower in rural areas than in Tokyo + Kyoto. When compared with the values reported in the literature, Pb exposure levels among Asian populations appear to be similar to the levels in Europe and in the United States, whereas Cd exposure seems to be higher in Asia than in Europe. The contribution of the dietary route in Pb absorption was variable and was inversely related to the extent of air pollution, whereas Cd uptake was almost exclusively via the dietary route with little contribution of the respiratory route.     

DNA damage by PAH and repair in a marine sponge

The sponge Tethya lyncurium from the Northern Adriatic has been used as an experimental species.A method is outlined for preparation of DNA which yields a highly purified DNA with a double-strand (ds) molecular weight of 25 M-dalton between single-strand (ss) breaks, which when properly damaged can be cut opposite to ss-breaks with nuclease s₁. The molecular weights of the resulting ds-DNA pieces and their distribution has been evaluated by electron microscope photographs.Sponges exposed to benzo[a]pyrene (BaP) in the dark only incorporate BaP-derivatives (BaPD) in small amounts, if any. However, in the presence of light, derivatization to BaP derivatives enables effective coupling to occur, as shown previously (R. K. Zahn et al., 1981). Sponges were exposed to radiolabeled BaP in the presence of light. Coupling of BaPD to the DNA as well as the induction of ss-breaks were measured.Light-mediated coupling is concentration dependent from 0.01 – 20 ppb BaP with a correlation coefficient of r = 0.84.Under conditions of possible repair, ss-breaks completely disappear from sponge DNA in the course of three weeks while a substantial fraction of the BaP derivatives persists.Double label experiments show that substantial DNA synthesis occurs during this time. Pollution causes a decrease of the molecular weight of unnicked DNA, re-incubation in clean water an increase. A DNA species of 24 M-dalton seems to play a critical role. If its percentage in the DNA population drops below a critical level, recovery is not longer possible. DNA damage by PAH and repair in sponges seems to differ from that of most eucaryotes.     

Personal exposure to benzene, toluene and xylene in different microenvironments at the Mexico City metropolitan zone

The Mexico City Metropolitan Zone (ZMCM) population's exposure to benzene, toluene and xylene was measured at different microenvironments to establish basic indicators of the presence and effects of these characteristic volatile organic compounds (VOC). In particular, VOC personal exposures were measured in different microenvironments during a 5-day working week, with 12-h daily periods. We have found a good agreement of our results with the registered VOC levels of the Metropolitan Automated Monitor System (RAMA) for the corresponding period. From our results, we expect to generate useful information to evaluate the health effects of these VOCs on exposed people.     

Effects of low-level exposure to xenobiotics present in paints on oxidative stress in workers

Paints are composed of an extensive variety of hazardous substances, such as organic solvents and heavy metals. Biomonitoring is an essential tool for assessing the risk to occupational health. Thus, this study analyzed the levels of biomarkers of exposure for toluene, xylene, styrene, ethylbenzene, and lead, as well as the oxidative stress biomarker alterations in painters of an industry. Lipid peroxidation biomarker (MDA), δ-aminolevulinate dehydratase (ALA-D), nonprotein thyol groups, superoxide dismutase and catalase (CAT) were analyzed in exposed and nonexposed subjects. We estimated which of the paint constituents have the greatest influence on the changes in the biomarkers of oxidative stress in this case of co-exposure. The results demonstrated that despite the fact that all the biomarkers of exposure were below the biological exposure limits, the MDA levels and antioxidant enzyme activities were increased, while nonprotein thyol groups and ALA-D levels were decreased in painters when compared with nonexposed subjects. After statistic test, toluene could be suggested as the principal factor responsible for increased lipid peroxidation and inhibition of ALA-D enzyme; however, further studies on the inhibition of ALA-D enzyme by toluene are necessary.     

Bioreactivity of municipal solid waste landfill leachates-Hormesis and DNA damage

The issue of domestic waste is recognised as one of the most serious environmental problems facing the nation. With the UK producing 35 million tonnes of municipal solid waste per annum, an understanding of the ranges of toxicity of landfill emissions is crucial to determine the degree of concern we should have about the potential effects these waste sites could have upon nearby populations and the surrounding environment. The aim of this study was to evaluate the bioreactivity of landfill leachates in terms of their capacity to damage ROS-sensitive bacteriophage plasmid DNA and induce toxicity in a commercial photobacterium toxicity assay, based on the light emission of Vibrio fischeri bacteria (ROTAS). The bacterial assay revealed widespread biostimulation and a hormesis response in the bacteria, with alpha-, beta- and gamma-response curves observed following exposure to the different landfill leachates. Different biological mechanisms lead to variations in bioreactivity, as seen in the plasmid DNA scission and ROTAS assays.     

Potential dermal exposure to deltamethrin and risk assessment for manual sprayers: influence of crop type

A comparison of the Potential Dermal Exposure (PDE) of workers to the insecticide deltamethrin was made as a function of crop type, in small agricultural production units in Argentina. Seven experiments were done with two different crops (maize and broccoli, treated area between 600 and 1000 m(2)) with three different operators under typical field conditions using a lever operated knapsack. The methodology is based on the whole body dosimetry technique, presenting separately the data for mixing/loading and application activities. These results indicate a higher concentration of pesticide in lower body sections for broccoli and a wider distribution for maize. The risk inherent in these agricultural procedures is estimated through Margin of Safety (MOS) values and was found to be generally safe. Preliminary results of a mass balance distribution of the pesticide between crop, soil and operator are also presented.     

残余应力对焊接部位疲劳破坏的影响

简要分析了影响焊接疲劳强度的主要因素,详细阐述了残余应力对焊接部位疲劳的影响,并将焊接残余应力的形成、分类进行了说明,最后经讨论提出必须重视残余应力对疲劳的影响,以保证钢结构使用性能。     

The use and abuse of chromosomal aberrations as an indicator of genetic damage

There are now many systems available for obtaining quick qualitative and quantitative assessments of chromosomal aberrations induced by various agents, and a number of these are being widely used as screening methods for possible genetic hazards.

Qualitative studies are valid provided that (a) observation is not confined to any one test system, and (b) care is taken to ensure that aberrations observed are not the result of the experimental methods employed. However, the direct relationship of the gross structural changes that are observable, and the production of “heritable mutation” is not necessarily as clear as is often supposed.

Very many quantitative studies are open to serious objection on the grounds that little or no thought has been given either to the time and mode of action of the compound under test in relation to the cell cycle, or to the profound perturbations which mutagens produce in the cell population. Often long treatments are given, and the same single fixation time (usually some hours after treatment) used for all “doses”. In such experiments it is certain that the cellular populations are so changed by the time assessment is made that reliable estimates of aberration frequency cannot be obtained.

These points are illustrated by reference to work with radiomimetic chemicals in plant cells, and some conclusions about experimental design for meaningful results drawn.