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1.
BACKGROUND: Workers in foundry and pottery are exposed to a mixture of chemicals and silica, which is suspected to cause genetic alterations. METHODS: To investigate the potential hazard associated with the occupational exposure to silica, DNA damage in the peripheral lymphocytes of 30 foundry and 22 pottery workers were examined by the alkaline single-cell gel electrophoresis or Comet Assay, and compared to 52 healthy subjects with no history of occupational silica or chemical exposure. RESULTS: The DNA damage observed in the lymphocytes of both foundry and pottery workers was significantly higher than that in their controls. Cigarette smoking was also related to DNA damage since the DNA damage observed in smoking silica-exposed workers compared with the non-smoking workers was significantly higher. CONCLUSIONS: Occupational exposure of silica from foundry and pottery workplaces has been associated with the increased DNA damage and smoking which represents an additional risk factor and must be avoided.  相似文献   

2.
The aim of this study was to provide data on genetic hazards associated with occupational exposure to low doses of ionising radiation in nuclear medicine departments. The DNA damage in peripheral blood lymphocytes of medical staff was assessed using the chromosome aberration test. Altogether 120 subjects (60 exposed and 60 controls) participated in the study. The exposed subjects showed significantly higher frequencies of chromosome aberrations than controls. Significant inter-individual differences in DNA damage within the exposed population indicate different genome sensitivity. Age and sex were not confounding factors, while smoking increased DNA damage only in control subjects. This study suggests that chronic exposure to low doses of ionising radiation in nuclear medicine departments causes cytogenetic damage. For this reason, exposed medical personnel should minimise radiation exposure wherever possible. Our results also point to the significance of biological indicators, which provide information about the actual risk for the radiation-exposed individuals.  相似文献   

3.
Despite much research over the last few decades, there still remains considerable uncertainty as to the genetic impact of ionizing radiation on human populations, particularly at low levels. The aim of the present study was to provide data on the genetic hazards due to occupational exposure of low doses of ionizing radiation in nuclear medicine departments. The assessment of primary DNA damage in peripheral blood leukocytes of medical staff was performed using the alkaline comet assay and the data obtained were compared with the results of conventional cytogenetic biodosimetry using the chromosome aberration (CA) test. Altogether 120 subjects (60 exposed and 60 controls) participated in the study. Statistically significant increases in primary DNA damage and increased frequencies of CAs compared to controls were observed. Within the exposed population, significant inter-individual differences in DNA damage were found, indicating differences in genome sensitivity. Age and gender were not confounding factors, while smoking enhanced the levels of primary DNA damage only in control subjects, as revealed by both biomarkers studied. The present study suggests that genotoxic damage results from exposure to chronic low doses of ionizing radiation in nuclear medicine departments. Therefore, the exposed medical personnel should carefully comply with the radiation protection procedures and should minimize radiation exposure where possible to avoid potential genotoxic effects. The results obtained in this study point to the significance of biological indicators providing information on the actual risk to the radiation exposed individuals. According to our results, the alkaline comet assay and CA test are sensitive biomarkers that can be used as additional complements to physical dosimetry for assessing exposure to radiation in nuclear medicine personnel.  相似文献   

4.

Objectives

The aim of this study is to assess chromosomal damage in Tunisian hospital workers occupationally exposed to low levels of ionizing radiation (IR).

Materials and Methods

The cytokinesis-block micronucleus (CBMN) assay in the peripheral lymphocytes of 67 exposed workers compared to 43 controls matched for gender, age and smoking habits was used. The clastogenic/aneugenic effect of IR was evaluated using the CBMN assay in combination with fluorescence in situ hybridization with human pan-centromeric DNA in all the exposed subjects and controls.

Results

The study showed a significant increase of the micronucleus (MN) frequency in the lymphocytes of the exposed workers compared to the control group (13.63±4.9‰ vs. 6.52±4.21‰, p < 0.05). The centromere analysis performed in our study showed that MNs in hospital staff were predominantly centromere negative (72%) and the mean negative labeled micronucleus (C-MN) frequency was significantly higher in the exposed subjects than in the controls (9.04±4.57‰ vs. 1.17±0.77‰). The multivariate regression analysis, taking into account all confounding factors, showed that only the time of exposure to IR had a significant effect on the level of MNs and C-MN.

Conclusion

The present study shows that chromosomal damage leading to the formation of micronucleated lymphocytes is more frequent in the hospital workers exposed to IR than in the controls, despite the low levels of exposure. The results of the study confirm the well-known clastogenic properties of ionizing radiation. In regards to health monitoring, detection of early genotoxic effects may allow for the adoption of preventive biological control measures, such as hygienic improvements in the workplace or reduction of hours of occupational exposure.  相似文献   

5.
The authors aimed to assess genotoxic damage in the lymphocytes of workers chronically exposed to ionizing radiation. The studied population included 15 exposed donors of the radiology unit of a public hospital in La Plata, Argentina. The control group included 15 nonexposed employers from administrative areas that the authors matched by age, sex, and smoking habits. The mean frequency of cytogenetic damage was higher in the exposed group than in the unexposed group for aneuploidy and structural chromosome aberrations. They observed the highest difference when achromatic lesions (or gaps) were considered. The comet assay showed that the frequency of cells with low damage was higher in the exposed group than in the unexposed group. A mean length analysis showed significant differences between exposed and nonexposed people. The results can be considered to be consistent evidence of occupational radiation exposure, and the results indicate that the workers must be advised to avoid or minimize their exposure.  相似文献   

6.
The authors aimed to assess genotoxic damage in the lymphocytes of workers chronically exposed to ionizing radiation. The studied population included 15 exposed donors of the radiology unit of a public hospital in La Plata, Argentina. The control group included 15 nonexposed employers from administrative areas that the authors matched by age, sex, and smoking habits. The mean frequency of cytogenetic damage was higher in the exposed group than in the unexposed group for aneuploidy and structural chromosome aberrations. They observed the highest difference when achromatic lesions (or gaps) were considered. The comet assay showed that the frequency of cells with low damage was higher in the exposed group than in the unexposed group. A mean length analysis showed significant differences between exposed and nonexposed people. The results can be considered to be consistent evidence of occupational radiation exposure, and the results indicate that the workers must be advised to avoid or minimize their exposure.  相似文献   

7.
OBJECTIVES: To study whether sewage workers are exposed to genotoxic substances. An increased risk of cancers among sewage workers has been noted. If this increased risk is due to an exposure to genotoxic agents, primarily DNA damage could be used as a biological marker of exposure. METHODS: In a cross sectional study, DNA damage in peripheral lymphocytes from 35 sewage workers and 30 controls was compared with alkaline single cell gel electrophoresis, a technique for detecting single strand breaks and alkali labile sites in DNA. The controls were selected from among municipal workers matched for age and smoking habit. Information about occupational exposures and possible confounders was collected by means of a questionnaire. RESULTS: No increase in DNA damage was found among the sewage workers when compared with the unexposed controls. CONCLUSIONS: The failure to detect increased damage to DNA in peripheral lymphocytes by alkaline single cell gel electrophoresis suggests that the sewage workers studied here were not exposed to genotoxic agents to a greater extent than other municipal workers. It may be, however, that the lymphocyte is not the appropriate target cell to study, or that sewage workers are exposed to carcinogens which do not damage the genetic material.  相似文献   

8.
Hospital workers are occupationally exposed to various agents known or suspected to induce chromosome damage, the most studied being ionizing radiation. To determine the extent of chromosome damage in peripheral blood lymphocytes in this population, taking into account temporal changes and job titles, a re-analysis of cytogenetic studies performed in four Italian laboratories in the period 1965–1993 was carried out. A total of 871 hospital workers and 617 controls, mainly coming from ad hoc studies or surveillance programs in occupational groups potentially exposed to ionizing radiation, were examined. The exposed to controls frequency ratio of chromosome aberrations was evaluated as the measure of effect within each dataset by job title, using multivariate Poisson regression analysis, which allowed an efficient control of confounding. Increased frequency of chromosome-type aberrations among exposed subjects was found in all datasets, especially in those dealing with older data. Significantly higher frequencies are reported for various job titles, particularly for orthopedists, radiologists, anesthesists, and nurses among paramedical occupations. Decrease in exposure to ionizing radiation in hospital workers was documented through a targeted study in the critical group of radiologists. A similar time-related reduction in the frequency of chromosome-type aberrations also has been reported by the surveillance studies carried out over the most recent decades. These data substantiate the use of chromosome-type aberrations as biomarkers of exposure in this occupational setting in the period evaluated. However, the increases observed also in workers with doubtful exposure to ionizing radiation indicate that other chromosome-damaging agents may be involved and, in turn, suggest the extension of surveillance to a larger number of occupations. Am. J. Ind. Med. 31:353–360, 1997. © 1997 Wiley-Liss, Inc.  相似文献   

9.

Purpose

We investigated genotoxic effects of occupational exposure to lead acetate in pottery-glaze ceramic workers.

Methods

The study was carried out in 30 exposed workers and 30 matched controls, to whom several biochemical parameters—the blood lead (B-Pb; range: exposed, 41.68–404.77; controls, 12–52) and cadmium (B-Cd) level, the activity of delta-aminolevulinic acid dehydratase (ALAD), erythrocyte protoporphyrin (EP), the level of vitamin B12 and folate in serum—were measured. The genotoxic effects were evaluated by the alkaline comet assay, the DNA diffusion assay and micronucleus test in peripheral blood lymphocytes.

Results

Subjects exposed to lead had significantly higher B-Pb level and, consequently, increased values of tail intensity (TI), frequency of apoptotic and necrotic cells, and frequency of micronuclei (MN). In contrast, their activity of ALAD, the level of vitamin B12 and folate in serum were significantly lower compared to controls. Poisson regression analysis showed a significant correlation of profession, duration of exposure, smoking, level of cadmium in blood, ALAD and EP with primary DNA damage. A majority of primary damage repairs in a short period after exposure to a genotoxic agent. In addition, the influence of gender and level of vitamin B12 and folate in serum MN frequency in exposed group was observed.

Conclusions

In this study, DNA diffusion and micronucleus test showed higher influence of tested parameters to DNA damage. The results indicate a need for concomitant use of at least two different biomarkers of exposure when estimating a genetic risk of lead exposure.  相似文献   

10.
Objectives: This study evaluates by comet assay the induction of early DNA damage in healthcare workers of an oncology hospital regularly handling antineoplastic drug mixtures. The aim was to identify a suitable biomarker of DNA damage by exposure to low levels of such drugs. Methods: We studied 12 day hospital nurses and 13 oncology ward nurses who performed up to 300 and up to 35 drug administrations per week, respectively, and five pharmacy employees who regularly prepared mixtures of antineoplastic agents. Thirty healthy subjects were selected as controls. For exposure evaluation, we performed environmental monitoring of 5-fluorouracil, cytarabine, gemcitabine, cyclophosphamide, and ifosfamide in selected work areas of pharmacy and day hospital units and biological monitoring of urine for the 5-fluorouracile metabolite, α-fluoro-β-alanine. We evaluated early DNA damage in lymphocytes and exfoliated buccal cells by comet assay measuring tail moment (TM) parameter that indirectly indicates the presence of DNA damage. Results: Environmental monitoring detected cyclophosphamide, 5-fluorouracil and ifosfamide, with higher levels of contamination in day hospital unit. The biological monitoring measured detectable levels of α-fluoro-β-alanine only in three nurses. Comet assay showed an increase on exfoliated buccal cells, even if not statistically significant, of mean TM with respect to controls in day hospital nurses (43.2 vs. 28.6, respectively) while ward nurses and pharmacy technicians did not show differences. Comet assay performed on lymphocytes did not show appreciable differences between exposed and controls. Conclusions: The employment of the sensitive comet assay, which is able to detect early the effects of a recent exposure to genotoxic substances, allowed us to find a slight DNA damage, only on exfoliated buccal cells of day hospital nurses, the group handling the highest amount of drugs during the administration process. This finding suggests that comet assay on exfoliated buccal cells could represent a useful tool to evaluate early and still repairable genotoxic effects of exposure to antineoplastic drug mixtures and then contribute to the improvement of the hospital safety practices.  相似文献   

11.
A population-based case-control study was conducted with 338 patients less than 15 years of age who were diagnosed with a primary tumor of the central nervous system from January 1968 through December 1977 in 53 contiguous New York counties. The study also included 676 controls who were selected from the birth certificate files of the New York State Department of Health. Parental occupational exposures at the time of each child's birth and at the time of tumor diagnosis were derived from maternal interviews. The current data set failed to show any consistent association between childhood central nervous system tumor risk and paternal occupational exposures to hydrocarbons or to electromagnetic fields, or employment in the aerospace industry or pulp and paper manufacturing. Findings for occupational exposures to ionizing radiation were also inconsistent. A positive association was observed between central nervous system tumor risk and paternal exposures to ionizing radiation based on industrial codes. Odds ratios ranged from 1.71 to 2.15. This association was not observed when paternal occupational titles were used to define exposure (range of odds ratios, 1.01-1.10). Maternal exposures to ionizing radiation were not related to risk regardless of the classification scheme used.  相似文献   

12.
Reactive oxygen species are important mediators of both mineral dust-induced (malignant) lung disease and in vitro DNA damage. Therefore, we studied in vivo oxidative DNA damage in coal workers who had been chronically exposed to silica-containing dust. In peripheral blood lymphocytes of 38 retired coal miners (eight with coal workers pneumoconiosis, 30 references) and 24 age-matched, non-dust-exposed controls 7-hydro-8-oxo-2-deoxyguanosine (8-oxodG) was determined by reversed phase high-performance liquid chromatography with electrochemical detection. The ratio of 8-oxodG residues to deoxyguanosine (dG) was related to individual cumulative dust exposure estimates and pneumoconiotic stage as established by chest radiography. The ratio of 8-oxodG to dG(x 10–5) in lymphocytes did not differ between miners with coal workers' pneumoconiosis (2.61 ± 0.44) and miners without coal workers' pneumoconiosis (2.96 ± 1.86). However, oxidative DNA damage in all miners was higher than in the non-dust-exposed controls (1.67 ± 1.31). 8-oxodG/dG ratio was not related to individual cumulative coal dust exposure, age or smoking (pack years) when evaluated by multiple linear regression. We suggest that oxidative damage to the DNA of peripheral blood lymphocytes may be introduced by increased oxidative stress responses in subjects chronically exposed to mineral dusts. Whether this is an important pathway in the suggested carcinogenicity of silica is still an open question.  相似文献   

13.
Damage to the microcirculation caused by high-dose ionizing radiation is well known but data concerning low-dose exposure are scant and contrasting. We employed capillary microscopy to study dermal microcirculation damage resulting from occupational exposure to ionizing radiation doses lower than 5 rem/year (maximum permissible dose in Italy). We studied 145 physicians (60.7% radiologists, 33.8% orthopedic specialists, 5.5% cardiologists) occupationally exposed to ionizing radiation and a control group of 106 subjects in comparable but different occupations not exposed to ionizing radiation or to other skin hazards. All subjects were administered a clinical protocol and underwent capillary microscopy of the fingernail-fold. Capillary microscopy alterations were classified as absent, mild, moderate, marked and severe. Our data confirm that occupational exposure to low-dose ionizing radiation can lead to morphological and functional alterations of the dermal microcirculation, which can be identified early by capillary microscopy. © 1996 Wiley-Liss, Inc.  相似文献   

14.
广州市交通警察淋巴细胞DNA损伤的研究   总被引:2,自引:0,他引:2  
目的研究交通警察的职业暴露与吸烟对淋巴细胞DNA损伤的影响.方法研究对象为广州市8个区的交通警共812人(男741人、女71人,其中内勤130人、外勤682人).静脉取血,以淋巴细胞分离液分离淋巴细胞.以彗星电泳的方法测定淋巴细胞DNA的损伤.结果未经校正的结果表明,内勤警平均年龄[(37.7±9.5)岁]较外勤警[(32.3±8.1)岁]大,且差异有显著性(P<0.01).性别(P=0.08)与年龄(P=0.45)对DNA损伤无影响.外勤警淋巴细胞彗星尾矩为4.20μm,95%CI为3.98~4.42μm,内勤警为3.23μm,95%CI为2.82~3.70μm,表明外勤警的DNA损伤较内勤警为重,差异有显著性(P<0.01).吸烟者淋巴细胞彗星尾矩为4.66μm,95%CI为4.37~4.97μm,不吸烟者为3.47μm,95%CI为3.21~3.75μm,而戒烟者则为3.28(2.57~4.17)μm,表明吸烟者的DNA损伤较戒烟者和不吸烟者为重,差异有显著性(P<0.01).在非吸烟者中,仅在家中的被动吸烟可使DNA损伤增加,但如果将外勤警除外,则工作场所的被动吸烟也可使DNA损伤增加.以协方差分析调整了各因素的影响,发现外勤警的职业、吸烟与女性性别可使淋巴细胞DNA损伤增加,且差异均有显著性(P<0.01).未发现年龄与被动吸烟对DNA损伤有影响.结论交通警的职业暴露与吸烟可使DNA损伤增加,女性交通警较男性交通警DNA损伤为重.  相似文献   

15.
目的 分别利用单细胞凝胶电泳技术 (SCGE)及染色体畸变试验观察电离辐射对作业人群外周血淋巴细胞DNA损伤作用和染色体损伤效应。方法 观察不同辐射剂量下外周血淋巴细胞DNA迁移长度及迁移率 ,同时观察不同剂量组下染色体畸变率及微核率。结果 各组染色体畸变率及微核率差异没有显著性 (P >0 0 5 ) ;接触射线的作业人群 ,彗星细胞率及DNA迁移长度明显超过对照组 ;同时 ,随着辐射剂量的加大 ,细胞DNA损伤级别亦有加重趋势。结论 SCGE技术可以检测电离辐射对作业人群的早期损害。  相似文献   

16.
In a case-control study, the authors investigated the association of parental occupational exposure to low-level external whole-body penetrating ionizing radiation and risk of congenital malformations in their offspring. Cases and controls were ascertained from births in two counties in southeastern Washington State, where the Hanford Site has been a major employer. A unique feature of this study was the linking of quantitative individual measurement of external whole-body penetrating ionizing radiation exposure of employees at the Hanford Site, using personal dosimeters, and the disease outcome, congenital malformations. The study population included 672 malformation cases and 977 matched controls from births occurring from 1957 through 1980. Twelve specific malformation types were analyzed for evidence of association with employment of the parents at Hanford and with occupational exposure to ionizing radiation. Two defects, congenital dislocation of the hip and tracheoesophageal fistula, showed statistically significant associations with employment of the parents at Hanford, but not with parental radiation exposure. Neural tube defects showed a significant association with parental preconception exposure, on the basis of a small number of cases. Eleven other defects, including Down syndrome, for which an association with radiation was considered most likely, showed no evidence of such an association. When all malformations were analyzed as a group, there was no evidence of an association with employment of the parents at Hanford, but the relation of parental exposure to radiation before conception was in the positive direction (one-tailed p value between 0.05 and 0.10). Given the number of statistical tests conducted, some or all of the observed positive correlations are likely to represent false positive findings. In view of strong contradictory evidence, based on no demonstrated effects in genetic studies of atomic bomb survivors in Hiroshima and Nagasaki, it is unlikely that these correlations result from a cause and effect association with parental radiation exposure.  相似文献   

17.
BACKGROUND: Although the aetiology of glioma is poorly understood, the higher incidence in males has long suggested an occupational cause. AIM: To investigate possible associations between occupational exposure to ionizing, ultraviolet (UV), radiofrequency (RF) and extremely low frequency (ELF) radiation and adult glioma risk. METHODS: Case-control study using histologically confirmed cases of glioma first diagnosed between 1987 and 1991 in Melbourne, Australia, matched by age, sex and postcode of residence. A detailed occupational history was obtained for each subject. Exposure to radiation was assessed using a Finnish job exposure matrix (FINJEM) for all the radiation types as well as self-reports and expert hygienist review for RF and ionizing radiation. For ELF and UV, gender-specific FINJEM analysis was performed. RESULTS: The study population consisted of 416 cases of glioma and 422 controls. The risk estimates given by FINJEM for ELF, RF and ionizing radiation were close to or below unity. Gender-specific analysis for UV showed odds ratios of 1.60 [95% confidence interval (CI) 0.95-2.69] and 0.54 (95% CI 0.27-1.07) for the highest exposed group of men and women, respectively (corresponding P value for trend was 0.03 and 0.04). CONCLUSIONS: We did not find evidence of an association between glioma and occupational exposure to ELF, RF and ionizing radiation. UV radiation was associated with increased glioma risk for men but this result could have been confounded by other predominantly male occupational and lifestyle exposures associated with high UV. Further investigation of UV radiation and glioma risk is suggested.  相似文献   

18.
目的:设计一种X射线机适用的防意外曝光语音指令系统,其智能防意外曝光功能可避免因意外曝光而导致对工作人员及候诊患者的辐射损害。方法:利用51单片机、无线发射及接收模块、继电器、语音控制器及门磁开关等配件,设计并组装X射线机适用的语音指令系统,通过给51单片机编程实现发出“语音”指令。结果:该系统能够自动感应内、外防护门开关状态,并将状态信号发送给51单片机,在操作曝光手闸时只有当内、外防护门均关闭时方能正常曝光,若防护门之一未完全关闭则禁止曝光,从而防止对工作人员或候诊患者造成意外辐射伤害。在曝光时可发出“呼吸”指令,指挥患者在检查中做相应配合。结论:智能X射线机防意外曝光语音指令系统能够防止在未正常关闭防护门状态下进行X射线检查,能有效防止工作人员和患者受到意外辐射伤害。该系统兼有的“呼吸”指令功能,能够自动指挥患者配合工作人员进行检查,以降低工作人员的工作强度。  相似文献   

19.
From the registry of self employed workers living in Paris, a group of 105 dental technicians was studied to evaluate occupational exposure, to determine respiratory manifestations, and to investigate immune disturbances. Seventy one dental technicians (age range 43-68: group D), 34 dental technicians younger than 43 or older than 68 (group d), and 68 control workers (age range 43-66: group C) were investigated. The demographic characteristics and the smoking habits of the groups D and C did not differ significantly. The dental technicians often worked alone (43.7%) or in small laboratories without adequate dust control. The mean duration of their exposure was long (group D 34.0 (SD 8.4) years). The prevalence of respiratory symptoms did not differ between groups D and C except for the occurrence of increased cough and phlegm lasting for three weeks or more over the past three years (group D 16.9%, group C 2.9%, p < 0.007). The effect of cigarette smoking on respiratory symptoms and lung function was obvious. All mean values of lung function for dental technicians and controls were within normal limits. Significant decreases in all mean lung function values were found among smokers by comparison with non-smokers, however, and a positive interaction with occupational exposure was established. The x ray films of dental technicians (n = 102, groups D and d) were read independently by four readers and recorded according to the International Labour Office classification of pneumoconioses. The prevalence of small opacities greater than 1/0 was 11.8% with a significant increase with duration of exposure. The prevalence among dental technicians with 30 years or exposure or more was significantly higher (22.2%) than those with less than 30 years (3.5, p < 0.004). The prevalence of autoantibodies (rheumatoid factors, antinuclear antibodies, and antihistone antibodies) was not significantly different in the groups D and C. When positive, autoantibodies only occurred at low concentrations. This finding contrasts with previous reports on the occurrence of autoantibodies and even of connective tissue diseases in dental technicians. In conclusion, the study confirms an increased risk of pneumoconiosis among dental technicians. Moreover, there may be other lung disorders such as impairment of lung function especially in association with cigarette smoking.  相似文献   

20.
目的 探讨焦炉作业工人多环芳烃 (polycyclicaromatichydrocarbon ,PAHs)暴露与其外周血淋巴细胞DNA损伤的关系。方法 选取 2 35名焦炉作业工人和 30名非职业PAHs暴露者 ,使用碱性单细胞凝胶电泳技术评价外周血淋巴细胞DNA损伤 ,采用高效液相色谱法测定工作周末班后 6h尿中 1 羟基芘水平 ,收集个人职业暴露、年龄、性别、吸烟和饮酒等信息。结果 焦炉工外周血淋巴细胞的Olive尾矩高于对照组 [数值分别为 2 .4 7(0 .2 2~ 4 6 .6 8)、0 .94 (0 .4 2~ 4 .2 1) ],差异有显著性 (P <0 .0 1) ,且与尿中 1 羟基芘水平呈相关性 (Spearman偏相关系数 =0 .2 2 ,P <0 .0 1)。以非暴露者Olive尾矩的上 5分位数 1.9作为判断个体是否为DNA损伤阳性的界值 ,焦炉工发生外周血淋巴细胞DNA损伤阳性的OR =5 .38,95 %CI=2 .0 7~ 14 .0 8,且随外暴露等级或内剂量水平的增高而呈增加的趋势。结论 焦炉工PAHs暴露水平与外周血淋巴细胞DNA损伤呈良好的剂量 -效应和剂量 -反应关系。  相似文献   

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