三氯乙烯对L-02肝细胞中SET相互作用蛋白eEF1A1、eEF1A2和DDB1 mRNA表达水平的影响

目的： 探讨人L-02肝细胞经三氯乙烯(TCE)染毒后SET相互作用蛋白eEF1A1、eEF1A2和DDB1 mRNA表达水平的变化。方法：取对数生长期的L-02肝细胞,暴露于不同浓度TCE(1.0、2.0、4.0、8.0 mmol/L)中,以DMSO为溶剂对照。24 h后,采用实时荧光定量PCR检测eEF1A1、eEF1A2和DDB1 mRNA表达水平。结果：与对照组相比,不同浓度的TCE均能够使L-02肝细胞eEF1A1、eEF1A2和DDB1 mRNA表达水平发生明显变化。其中,DDB1和eEF1A2 mRNA表达水平在低浓度(1.0 mmol/L)TCE暴露下显著升高,而随着TCE浓度的升高其mRNA表达水平显著降低(P<0.05或P<0.01)。eEF1A1 mRNA表达水平随着TCE浓度的增加而升高(P<0.05)。结论：TCE染毒可诱发L-02肝细胞中SET相互作用蛋白的mRNA表达水平发生改变。     

Renal cell cancer risk and occupational exposure to trichloroethylene: results of a consecutive case-control study in Arnsberg,Germany

BACKGROUND: German studies of high exposure prevalence have been debated on the renal carcinogenicity of trichloroethylene (TRI). METHODS: A consecutive hospital-based case-control study with 134 renal cell cancer (RCC) cases and 401 controls was conducted to reevaluate the risk of TRI in this region which were estimated in a previous study. Exposure was self-assessed to compare these studies. Additionally, the job history was analyzed, using expert-based exposure information. RESULTS: The logistic regression results, adjusted for age, gender, and smoking, confirmed a TRI-related RCC risk in this region. Using the database CAREX for a comparison of industries with and without TRI exposure, a significant excess risk was estimated for the longest held job in TRI-exposing industries (odds ratio (OR) 1.80, 95% confidence interval (CI) 1.01-3.20). Any exposure in "metal degreasing" was a RCC risk factor (OR 5.57, 95% CI 2.33-13.32). Self-reported narcotic symptoms, indicative of peak exposures, were associated with an excess risk (OR 3.71, 95% CI 1.80-7.54). CONCLUSIONS: The study supports the human nephrocarcinogenicity of trichloroethylene.     

胆红素对TCE致ICR小鼠DNA损伤的拮抗作用

目的：研究胆红素对三氯乙烯(TCE)致ICR小鼠肝、肾、外周血DNA损伤的影响。方法：应用单细胞凝胶电泳(SCGE)技术，检测TCE对ICR小鼠肝、肾、外周血细胞DNA损伤作用，同时观察20-200μmol／L胆红素对TCE所致DNA损伤的保护作用。结果：TCE染毒组肝、肾、血细胞彗星率较对照组增加；胆红素各剂量组SCCE各指标在20-200μmol／L范围内先减小后增大，100μmol／L处最小。结论：100μmol/L左右的胆红素能较好的拮抗TCE对小鼠肾脏细胞DNA损伤。     

银杏叶提取物对三氯乙烯所致的角质形成细胞线粒体膜电位变化的影响

目的研究三氯乙烯(TCE)对角质形成细胞(KC)线粒体膜电位的影响以及银杏叶提取物(GBE)的保护作用,为预防三氯乙烯皮肤损害提供理论依据。方法体外培养的人角质形成细胞以不同浓度TCE处理8h,GBE保护实验则以不同浓度GBE预处理2h后再进行TCE染毒,采用罗丹明123(Rh123)和碘化丙啶(PI)双染色方法,通过流式细胞仪检测线粒体膜电位的变化情况。结果空白对照组Rh123荧光强度为18.73±0.45,正常和早期凋亡细胞分别占(77.10±2.08)%和(12.33±1.39)%;2.0mmol/LTCE染毒组Rh123荧光强度下降到8.20±0.66(与空白对照相比,P<0.01),正常和早期凋亡细胞比例分别为(11.90±0.56)%和(65.33±1.45)%(与空白对照相比,均P<0.01)。10mg/L的GBE预处理对2.0mmol/LTCE所致的线粒体膜电位下降即显示有保护作用,Rh123荧光强度为13.80±0.92,正常细胞占(40.90±2.10)%,早期凋亡细胞占(32.10±1.25)%(与2.0mmol/LTCE染毒组相比差异有统计学意义,P<0.01)。随着GBE浓度的增大,保护作用渐强,100mg/L的GBE达到完全的保护作用,上述3项指标分别为18.57±0.57,(76.57±2.67)%和(11.63±1.07)%(与2.0mmol/LTCE染毒组相比,P<0.01,而与空白对照组相比差异均无统计学意义)。结论TCE可以剂量依赖性地诱导KC线粒体膜电位的下降,使细胞进入凋亡状态;GBE预处理能有效预防TCE所致的线粒体膜电位的下降,并可降低KC凋亡。研究结果提示GBE可能用作预防三氯乙烯皮肤损伤的有效保护剂。     

A meta-analysis of occupational trichloroethylene exposure and multiple myeloma or leukaemia

BACKGROUND: Trichloroethylene (TCE) has been widely used as an industrial solvent and degreasing agent. AIMS: We conducted a meta-analysis of epidemiologic studies of occupational TCE exposure and multiple myeloma (MM) or leukaemia. METHODS: We identified a total of eight cohort or case-control studies that enumerated a TCE-exposed study population and presented relative risk (RR) estimates for MM (n = 7) and/or leukaemia (n = 7). The individual studies included aerospace or aircraft workers (n = 3 studies), workers from a transformer manufacturing plant (n = 1 study) and workers from numerous occupations who, based on biomonitoring or extensive industrial hygiene exposure measurements, were likely exposed to TCE (n = 4). We used random effects models to calculate summary relative risk estimates (SRRE). In addition, we examined heterogeneity across studies and the relative influence of each individual study on the overall meta-analysis. RESULTS: No association was observed for MM (SRRE = 1.05, 95% CI: 0.80-1.38; P value for heterogeneity = 0.94) or leukaemia (SRRE = 1.11, 95% CI: 0.93-1.32; P value for heterogeneity = 0.50), based on TCE-exposed subgroup meta-analyses. Study-specific RR estimates for MM ranged between 0.57 and 1.62. RRs for leukaemia ranged between 1.05 and 1.15 in five studies, while one study reported a 2-fold increased RR and another study reported an inverse association of 0.60. All confidence intervals (CIs) for study-specific estimates included 1.0. CONCLUSIONS: The results of this meta-analysis do not support an etiologic association between occupational TCE exposure and risk of MM or leukaemia.     

Trichloroethylene decreases heat shock protein 90 interactions with endothelial nitric oxide synthase: implications for endothelial cell proliferation.

Trichloroetheylene (TRI) is an environmental pollutant that has been linked to congenital heart defects (CHD). Endothelial nitric oxide synthase (eNOS) generation of nitric oxide (NO) plays an important role in endothelial cell proliferation, which is considered essential for normal blood vessel growth and development. We hypothesized that TRI alters the balance of NO and superoxide anion (O2-) to impair endothelial cell proliferation. Proliferating endothelial cells were pretreated with TRI (5 microM) and then stimulated with the calcium ionophore, A23187 (5 microM), to determine changes in endothelial cell and eNOS function with respect to NO and O2- generation. Immunoblots of eNOS, phospho-eNOS at serine 1179 (S1179), and the levels of associated heat shock protein 90 (hsp90) were used to define the activation state of eNOS. The effects of TRI (0.05-100 microM) on vascular endothelial growth factor (VEGF, 0.58 nM) induced endothelial cell proliferation were determined from cell counts. TRI decreased A23187-stimulated nitrite + nitrate production from 1.99 +/- 0.90 to 0.89 +/- 0.51 pmol/mg protein (p < 0.05; n = 6). In controls, Lomega-nitroargininemethylester (L-NAME) increased A23187-stimulated O2- production from 0.130 +/- 0.089 to 0.214 +/- 0.071 nmol/min/mg protein (p < 0.05; n = 5). In TRI-treated cultures, however, L-NAME decreased A23187-stimulated O2- production from 0.399 +/- 0.121 to 0.199 +/- 0.055 nmol/min/mg protein (p < 0.05; n = 5). TRI decreased hsp90 associated with eNOS by 46.7% and inhibited VEGF-stimulated endothelial cell proliferation by 12 to 35%. These data show that TRI alters hsp90 interactions with eNOS and induces eNOS to shift from NO to O2- generation. Our findings provide new insight into how TRI alters endothelial and eNOS function to impair VEGF-stimulated endothelial proliferation. Such changes in endothelial function may play an important role in the development of congenital heart defects.     

三氯乙烯对职业人群血浆中谷胱甘肽-S转移酶活性的影响

目的　探讨三氯乙烯(TCE)对职业人群血浆中谷胱甘肽-S转移酶(GST)活性的影响。方法　选择51名接触TCE的 职业工人及不接触TCE的20人作为对照,通过问卷调查收集每人的一般情况和职业史等。按调查表格逐项进行问诊、全面 体格检查,尿中三氯乙酸(TCA)浓度和血浆中GST活性的测定。结果　接触组内男性比女性接触TCE的时间长(P<0.01) 尿中TCA的浓度小(P<0.05)。接触组中男性和女性的尿中TCA的浓度均显著高于对照组(P<0.01)。对测定结果按接触 TCE工龄或尿中TCA浓度进行多次分组,血浆中GST活性未发现有统计意义的变化。结论　TCE对职业接触人群的血浆中 GST活性未产生有统计意义的改变,因此我们认为血浆中GST活性不能作为TCE对人体损害的早期观察指标。至于接触更 长时间或更高TCE浓度是否会产生有统计意义的变化,需要我们作进一步的研究。     

三氯乙烯对职业人群遗传指标的影响

目的确定三氯乙烯(Trichloroethylene,TCE)对人体遗传指标的影响,为控制TCE中毒的危害和确定早期诊断指标提供一定的依据.方法按调查表格逐项进行问诊、全面体格检查、尿中三氯乙酸(TCA)和遗传指标的测定.结果SCE细胞和慧里细胞(%)在接触TCE工龄小于2年时,与对照组并无统计学上的差异,P＞0.05;但在接触TCE工龄大于2年时,以上指标均显著高于对照组(P＜0.05).尿中TCA浓度小于50mg/L时,双微核率、微核率、SCE细胞与对照组并无统计学上的差异,P＞0.05;但在尿中TCA浓度大于50 mg/L时,以上指标均显著高于对照组(P＜0.05).结论TCE对职业接触人群的遗传指标确实产生了有统计学意义的改变,TCE具有一定的遗传毒性.可以考虑把遗传指标测定作为职业接触TCE人员职业性健康检查的检查项目,但需对更大人群的遗传指标进行测定,以确定正常参考值和早期损害的阚值.     

Momentary brain concentration of trichloroethylene predicts the effects on rat visual function.

The relationship between the concentration of trichloroethylene (TCE) in the brain and changes in brain function, indicated by the amplitude of steady-state pattern-elicited visual evoked potentials (VEP), was evaluated in Long-Evans rats. VEPs were recorded from visual cortex following stimulation of the eyes and, thus, reflect the function of the afferent visual pathway and, in broad terms, may be indicative of overall brain function. The concentration of TCE in the brain at the time of VEP testing (i.e., momentary brain concentration) was hypothesized to predict the amplitude of the VEP across a range of inhalation concentrations, both during and after exposure. Awake restrained rats were exposed to clean air or TCE in the following combinations of concentration and duration: 500 ppm (4 h), 1000 ppm (4 h), 2000 (2 h), 3000 ppm (1.3 h), 4000 ppm (1 h), and 5000 ppm (0.8 h). VEPs were recorded several times during the exposure session, and afterward for experimental sessions of less than 4 h total duration (i.e., concentrations from 2000 to 5000 ppm). The sample collection time for each VEP was about 1 min. Brain concentrations of TCE were predicted using a physiologically based pharmacokinetic (PBPK) model. VEP waveforms were submitted to spectral analysis, and the amplitude of the largest response component, occurring at twice the temporal stimulation rate (F2), was measured. Exposure to all air concentrations of TCE in the study reduced F2 amplitude. The reduction of F2 amplitude was proportional to momentary brain TCE concentration during and after exposure. A logistical function fit to the combined data from all exposure conditions described a statistically significant relationship with 95% confidence limits between brain TCE concentration and F2 amplitude. The results support the hypothesis that momentary brain concentration of TCE is an appropriate dose metric to describe the effects of acute TCE inhalation exposure on rat VEPs. The combination of the PBPK model predicting brain TCE concentration from the exposure conditions with the logistical function predicting F2 amplitude from the brain TCE concentration constitute a quantitative exposure-dose-response model describing an acute change in neurological function following exposure to an important hazardous air pollutant.     

Serum proteomic analysis reveals potential serum biomarkers for occupational medicamentosa-like dermatitis caused by trichloroethylene

Trichloroethylene (TCE) is an industrial solvent with widespread occupational exposure and also a major environmental contaminant. Occupational medicamentosa-like dermatitis induced by trichloroethylene (OMLDT) is an autoimmune disease and it has become one major hazard in China. In this study, sera from 3 healthy controls and 3 OMLDT patients at different disease stages were used for a screening study by 2D-DIGE and MALDI-TOF-MS/MS. Eight proteins including transthyretin (TTR), retinol binding protein 4 (RBP4), haptoglobin, clusterin, serum amyloid A protein (SAA), apolipoprotein A-I, apolipoprotein C-III and apolipoprotein C-II were found to be significantly altered among the healthy, acute-stage, healing-stage and healed-stage groups. Specifically, the altered expression of TTR, RBP4 and haptoglobin were further validated by Western blot analysis and ELISA. Our data not only suggested that TTR, RBP4 and haptoglobin could serve as potential serum biomarkers of OMLDT, but also indicated that measurement of TTR, RBP4 and haptoglobin or their combination could help aid in the diagnosis, monitoring the progression and therapy of the disease.