低浓度职业性苯乙烯接触对线粒体DNA拷贝数和微核率的影响研究

目的 探讨接触低浓度苯乙烯对线粒体DNA含量和微核率的影响,以寻找潜在的生物标志。方法 招募上海某塑料生产企业接触苯乙烯的男性工人127名为研究对象,检测工作车间空气中苯乙烯浓度,应用高效液相色谱法对苯乙烯的尿中代谢物进行检测,应用分光光度法测定尿中肌酐进行校正;按照尿中苯乙醇酸水平,将≤0.000 9 mg/g（以肌酐校正）者纳入低接触组,> 0.000 9～0.001 4 mg/g（以肌酐校正）者纳入中接触组,> 0.001 4 mg/g（以肌酐校正）者则纳入高接触组。通过实时荧光定量PCR实验检测工人外周血的线粒体DNA含量,通过胞质分裂阻滞微核实验检测外周血淋巴细胞的微核率。结果 工作场所定点采样显示环境空气中苯乙烯浓度低于1.2 mg/m3,尿中苯乙醇酸水平的中位数和四分位数为0.001 1(0.000 8,0.001 8)mg/g（以肌酐校正）。广义线性模型分析结果显示：与低接触组相比,中接触组工人的mtDNAcn（自然对数转换后）升高0.271(P=0.042);中性粒细胞计数与淋巴细胞计数比值每升高1个单位,mtDNAcn（自然对数转换后）降低0.227(P...     

煤矿工人外周血端粒长度和线粒体DNA拷贝数与高血压的关系研究

目的 分析煤矿工人中高血压与外周血端粒长度、线粒体DNA拷贝数（mtDNA-CN）的关系以及端粒长度与mtDNA-CN对高血压的交互作用。方法 2013年7-12月在山西省某煤矿集团开展病例对照调查研究,选取325名健康工人作为对照组,378名高血压工人作为病例组。通过问卷调查收集研究对象的一般人口学特征、生活行为习惯等信息;采用实时定量PCR检测外周血端粒长度、mtDNA-CN水平;运用logistic回归分析高血压与端粒长度、mtDNA-CN及其他因素的关系,采用相加、相乘模型分析端粒长度与mtDNA-CN对高血压的交互作用。结果 病例组工人的平均端粒长度为（1.50±0.55）kb,对照组工人的平均端粒长度为（2.01±0.62）kb,两组间的差异有统计学意义（t=11.68,P<0.001）;相关分析结果显示,在病例组,端粒长度与mtDNA-CN呈正相关（r=0.157,P=0.002）;多因素分析结果显示,端粒长度（OR=4.408,95% CI：3.012~6.452）、年龄（OR=0.417,95% CI：0.284~0.613）、BMI（OR=1.357,95% CI：1.162~1.584）、家庭月均收入（OR=0.656,95% CI：0.553~0.778）和工龄（OR=1.249,95% CI：1.100~1.417）均是高血压的影响因素;且端粒长度与mtDNA-CN对高血压有相乘交互作用（OR=1.267,95% CI：1.094~1.468）。结论 端粒长度较短是高血压的危险因素,端粒长度与mtDNA-CN对高血压的相乘交互作用存在,但未发现mtDNA-CN与高血压相关。     

接触低浓度苯系物对工人健康状况的影响

目的了解长期接触低浓度苯系物对工人健康的影响。方法设立接触组与对照组,并对两组人员进行血象、血压、心电图等项目的检查。同时测定接触作业环境中苯、甲苯、二甲苯的浓度。结果两组血压变化差异无显著性,心电图总异常率即各种异常心电图发生率经统计学分析差异无显著性,但心率失常（窦缓、窦速、早搏、传导阻滞、预激综合征）接触组与对照组对比差异有非常显著性（χ2=7.63,P〈0.01）,即心率失常发生率接触组明显高于对照组;血象中白细胞计数减少检出率接触组明显高于对照组;而血红蛋白含量、血小板计数减少差异无显著性。结论长期接触低浓度苯系物,可损害骨髓造血功能,引起白细胞减少。并可引起自主神经功能紊乱,导致心律失常。     

接触低浓度苯系物对工人健康状况的影响

目的了解长期接触低浓度苯系物对工人健康的影响。方法设立观察组与对照组,并对2组人员进行血像、血压、心电图等项目的检查。同时测定观察组作业环境中苯、甲苯、二甲苯的浓度。结果2组血压变化差异无统计学意义;心电图总异常率及各种异常心电图发生率经统计学分析差异无统计学意义,但心率失常（即窦缓、窦速、早搏、传导阻滞、预激综合征合计）观察组与对照组差异存在有统计学意义（χ^2=7．63,P〈0．01）,即心律失常发生率接触组明显高于对照组;血象中白细胞计数减少检出率明显高于对照组,而血红蛋白含量、血小板计数减少差异无统计学意义。结论长期接触低浓度苯系物,可损害骨髓造血功能,引起白细胞减少。并可引起自主神经功能紊乱,导致心律失常。     

低浓度苯及同系物对接触工人健康状况的影响

[目的]探讨低浓度苯及同系物对接触工人的健康危害,为今后防治苯的危害提供依据。[方法]对2个企业苯作业车间空气中毒物浓度进行测定,并对观察组和对照组工人进行健康体检。[结果]2个厂工作场所苯浓度短时间接触均值分别为1.03、1.93 mg/m^3,均低于国家职业卫生标准;观察组和对照组的临床症状检出率、心电图、X线胸片及血压异常率的差异均无统计学意义（P〉0.05）;接触组外周血白细胞减少31例,占27.0%,高于对照组,差异有统计学意义（P〈0.01）;观察组年龄和工龄分析表明,白细胞下降有随年龄和工龄增加而降低的趋势,但差异无统计学意义（P〉0.05）。[结论]低浓度的苯及同系物可对人体健康产生危害。     

外周血线粒体DNA拷贝数检测及影响因素

外周血线粒体DNA拷贝数（mtDNAcn）是反映机体氧化应激状态的新兴生物标志物,越来越多流行病学研究表明外周血mtDNAcn异常与心血管疾病、帕金森、恶性肿瘤等重大慢性疾病发生风险有关。因此,了解mtDNAcn的检测手段、寻找mtDNAcn这一疾病早期生物标志物的影响因素,对慢性病防控有着重要意义。本文针对外周血mtDNAcn相关检测技术和外周血mtDNAcn的影响因素研究进展进行综述,旨在为mtDNAcn疾病早期生物标志物的确定提供依据,为慢性病预防提供技术支撑。     

肿瘤循环线粒体DNA研究现状

近年来日益增多的研究表明,肿瘤在生长过程中会持续释放肿瘤细胞DNA进入外周血液。释放的DNA根据核基因和核外基因分为循环核DNA(nuclear acid,nDNA)和循环线粒体DNA(mitochondrial DNA,mtDNA)。目前,几乎所有研究都集中于循环nDNA,循环mtDNA鲜有关注。为此,我们从定性和定量两个方面,对国际上已报道的关于循环mtDNA方面的研究进行归类综述,初步探讨循环mtDNA在肿瘤发生发展中的生物学意义进行,阐明循环mtDNA在肿瘤诊断以及疗效监测中潜在的临床应用价值。     

低浓度苯接触工人尿中代谢产物与苯暴露浓度相关性分析

目的 分析低浓度苯接触工人尿中代谢产物苯巯基尿酸（s-phenylmercapturic acid,SPMA）和反-反式黏糠酸（trans,trans-muconic acid,t,t-MA）与苯暴露浓度的相关性。方法 2018年9月—2021年9月选择山东省某鞋厂和篮球厂共117名苯接触工人作为接苯组,80名鞋厂和食品厂不接触苯的工人为对照组。通过被动个体采样方式进行工人苯暴露浓度监测,收集工人班后尿并检测尿中SPMA和t,t-MA浓度。分析内、外暴露指标的相关性及相对内暴露指数（relative internal exposure index,RIE index）随空气苯暴露浓度的变化趋势。结果 苯接触组工人空气苯浓度在1.00～107.40 mg/m3之间,M(P25,P75)为4.14(2.71,6.63)mg/m3,71%的苯接触组工人空气苯浓度低于我国工作场所空气中苯时间加权平均容许浓度限值（6.00 mg/m3）,对照组工人空气苯浓度低于检出限值。苯接触组工人尿中代谢产物SPMA浓度、t,t-MA浓度与对照组尿中相应苯代谢产物浓度的差异均有统计学意义（均P<0.05...     

线粒体DNA拷贝数与燃煤污染型地方性氟中毒的关联分析

目的:探讨相对线粒体DNA拷贝数（mitochondrial DNA copy number,mtDNA-CN）与燃煤污染型地方性氟中毒（简称燃煤型地氟病）的关联。方法:2018年6月至2019年3月,采用横断面研究,在贵州省典型燃煤型地氟病病区毕节市选择482例燃煤型地氟病患者作为病例组;同时,在非病区长顺县选择21...     

职业接触低浓度苯同系物人群血细胞DNA损伤的研究

以接触苯的同系物作业工人78人作为接触组,31名饮食行业从业人员作为对照组.运用单细胞凝胶电泳进行外周血细胞DNA损伤的检测.在校正了年龄、吸烟水平后,接触组外周血细胞的彗星率、彗星尾长均高于对照组,且有统计学意义(P＜0.01).从接触工龄看,以1年为界,外周血细胞的彗星也有统计学意义(P＜0.01).提示职业性接触低浓度苯的同系物工人血常规、血生化指标均在正常范围时,可采用外周血彗星细胞率作为健康监护的生物监测指标,用于早期筛查.     

Increased mitochondrial DNA copy number in occupations associated with low-dose benzene exposure

Background: Benzene is an established leukemogen at high exposure levels. Although low-level benzene exposure is widespread and may induce oxidative damage, no mechanistic biomarkers are available to detect biological dysfunction at low doses.Objectives: Our goals were to determine in a large multicenter cross-sectional study whether low-level benzene is associated with increased blood mitochondrial DNA copy number (mtDNAcn, a biological oxidative response to mitochondrial DNA damage and dysfunction) and to explore potential links between mtDNAcn and leukemia-related epigenetic markers.Methods: We measured blood relative mtDNAcn by real-time polymerase chain reaction in 341 individuals selected from various occupational groups with low-level benzene exposures (> 100 times lower than the Occupational Safety and Health Administration/European Union standards) and 178 referents from three Italian cities (Genoa, Milan, Cagliari).Results: In each city, benzene-exposed participants showed higher mtDNAcn than referents: mtDNAcn was 0.90 relative units in Genoa bus drivers and 0.75 in referents (p = 0.019); 0.90 in Milan gas station attendants, 1.10 in police officers, and 0.75 in referents (p-trend = 0.008); 1.63 in Cagliari petrochemical plant workers, 1.25 in referents close to the plant, and 0.90 in referents farther from the plant (p-trend = 0.046). Using covariate-adjusted regression models, we estimated that an interquartile range increase in personal airborne benzene was associated with percent increases in mtDNAcn equal to 10.5% in Genoa (p = 0.014), 8.2% (p = 0.008) in Milan, 7.5% in Cagliari (p = 0.22), and 10.3% in all cities combined (p < 0.001). Using methylation data available for the Milan participants, we found that mtDNAcn was associated with LINE-1 hypomethylation (–2.41%; p = 0.007) and p15 hypermethylation (+15.95%, p = 0.008).Conclusions: Blood MtDNAcn was increased in persons exposed to low benzene levels, potentially reflecting mitochondrial DNA damage and dysfunction.     

低浓度混苯作业工人腹部超声检查结果

目的探讨长期在低浓度混苯（苯、甲苯、二甲苯）作业环境下,作业工人腹部超声影像上的变化。方法采用彩色多普勒超声显像仪,选择接触低浓度三苯的作业工人170人作为接触组。另选其他非接触三苯的在年龄、工龄、性别等构成方面无显著差异的人员170人作为对照组。接触组和观察组均进行肝、胆、脾、肾部位的超声检查,并对结果进行χ2检验。结果苯接触组腹部超声结果异常检出率（38.23%）明显高于对照组（13.52%）,差异有统计学意义（P〈0.05）。接触组在肝肿大、脂肪肝、脾肿大、肾结石超声结果异常检出率均高于对照组,差异均有统计学意义（P〈0.05）。且随着工龄的延长,以上个指标的超声检出率增高。接触组11~20 a工龄段的腹部B超异常检出率为40%,明显高于0~10年工龄组15.45%的异常检出率,差异有统计学意义（P〈0.05）。结论长期接触低浓度混苯作业工人的肝、脾和肾的B超声像图均易发生改变,是混苯作业人员早期发现腹部损害,保护机体健康的一种较好的监护检查方法 。     

Cytogenetic study of workers exposed to benzene

Cytogenetic evaluation of peripheral lymphocytes from 52 workers exposed to low levels of benzene (less than 10 ppm) has revealed an increase in aberration rates as compared to that of a 44-person group seen for preemployment examination. Statistically significant differences were found in the distribution of specific types of chromosomal aberrations. These induced-aberrations levels were not related to the age of the workers. Continued study of benzene-exposed workers (as well as industrial populations exposed to any clastogenic agent) with medical cytogenetic surveillance, environmental monitoring, and lifetime epidemiologic investigation is recommended.     

低浓度苯暴露对大鼠神经行为的影响

摘要:目的　研究低浓度气态苯吸入对大鼠学习记忆等神经行为的影响,并探讨低浓度苯吸入对大鼠血象的改变。方法　SD雄性大鼠随机分4组,每组10只,低、中、高剂量组苯染毒浓度分别为4 mg/m3、6 mg/m3和10 mg/m3,对照组吸入空气。采用静式吸入染毒法,4 h/d,5 d/w,持续染毒4 w,染毒结束后进行学习记忆等神经行为学测试、血象、嗜多染红细胞微核实验。结果　Morris水迷宫定位航行实验,高剂量组大鼠d 3、d 4的逃避潜伏期明显高于对照组（P＜0.05）,空间探索实验的目标象限时间明显低于对照组（P＜0.05）。高剂量组大鼠的后肢撑力指数明显高于对照组（P＜0.05）。低、中、高剂量组白细胞计数明显低于对照组（P＜0.05）。结论　低剂量、短时间暴露苯可损害大鼠学习记忆及运动功能,引起外周血白细胞计数降低。     

低浓度混苯作业女工及其幼儿健康的调查

本文调查低浓度混苯作业女工及其幼儿共18对的健康情况,与对照组18对出较。调查项目包括询问女工的职业史、月经史、生育史和幼儿情况,进行体捡,以及血细胞、胎儿血红蛋白、血红蛋白A_2、外周淋巴细胞微核率和姐妹染色单体交换频率等实验室检查。结果除苯组女工的血色素、白细胞数均值和苯组幼儿血色素均值显著低于对照组外,其余两组比较无显著性差异。提示低浓度笨可能对作业女工造血系统产生损害,其他方面尚无明显影响。     

Analysis of chromosomal aberrations in workers exposed to low level benzene

Metaphase chromosome preparations were analysed as part of a larger study from a population occupationally exposed to benzene and compared with a control group. Forty eight of the 66 exposed individuals and 29 of the 33 controls had samples in which metaphase spreads could be evaluated. The incidence of chromosomal aberrations (particularly chromatid deletions and gaps) in the exposed group were slightly increased compared with the control group. This increase was of borderline significance in parametric statistical tests but was significant using Fisher's exact test. No lifestyle factors had any consistent effect on the incidence of chromosome aberrations, although there was a small reduction in gaps with increasing cigarette smoking. Older individuals had a higher incidence of chromosome exchanges and "other" aberrations. Individuals who reported a recent viral illness had a higher incidence of aberrations particularly gaps. There was no evidence of any correlation in the incidence of chromosome aberrations with any of the other biological parameters previously reported. The increased incidence of aberrations seen in the group exposed to benzene may result from a history of exposure to benzene. Nevertheless, other explanations such as sampling, interindividual variability, and unintentional bias in the selection of two groups cannot be excluded.     

高浓度接苯工人血小板减少17例的临床分析

目的探讨在较短时间、接触高浓度苯作业工人早期血小板减少的发病机制。方法选择某私营箱包厂从事喷胶、打钉工种并有单纯血小板减少的工人17名为观察组进行流行病学调查,详细询问其职业史、既往史、临床表现,检测周围血细胞、骨髓象、T细胞亚群及血小板相关抗体PAlgG、PAlgM、PAlgA。选择某电子有限公司非毒物接触工人20名为对照组。结果观察组中T细胞亚群CD3+、CD4+、CD8+、CD4+／CD8+分别为57．80％±2．51％、26．33％±2．52％、32．18％±13．60％及0．79％±0．12％;血小板相关抗体测定PAlgG、PAlgM、PAlgA分别为298±42．6、98．6±22．6、40．2±9．65,与对照组比较差异有统计学意义(P<0．01)。结论在较短时间、高浓度接苯工人的外周血可仅以血小板减少为早期改变,其发病机制与免疫功能紊乱有关,临床表现为免疫性血小板减少性紫癜。     

Cohort study among workers exposed to benzene in China: II. Exposure assessment

This report describes a retrospective exposure assessment method used in a follow-up mortality study of workers exposed to benzene. The approach quantified historical exposure to benzene in a multi-industry, multicenter cohort, involving 672 factories in 12 cities in China. Historical exposure data were collected to obtain exposure information related to 1,427 work units (departments) and 3,179 unique job titles from benzene-producing or -using factories in which written records and other data sources were evaluated. The basic unit for exposure assessment was a factory/work unit/job title combination which was considered separately during each of seven calendar-year time periods between 1949 and 1987 for a total of 18,435 exposure assignments. Historical information collected to estimate exposure included benzene monitoring data; lists of raw materials and factory products, and the percentage of benzene in each; the total amount and dates of use of benzene or benzene-containing materials; use of engineering controls and personal protective equipment; and other available exposure information. Overall, 38% (ranging from 3% for the earliest periods to 67% for the last period) of the estimates were based primarily on benzene monitoring data. In the absence of job-specific benzene monitoring data for a given calendar period, measurement results or exposure estimates for similar jobs and/or other calendar periods were used in conjunction with other exposure information to derive estimates. Estimated exposure levels are presented by industries and occupations. The highest average exposures during 1949–1987 were observed for the rubber and plastic industry (30.7 ppm), and for rubber glue applicators (52.6 ppm).     

Genotoxic effects in workers exposed to low levels of benzene from gasoline

To study genotoxic effects of exposure to low levels of benzene, single-strand breaks (SSB) in DNA of leukocytes and urinary levels of the oxidative DNA adduct 8-hydroxydeoxyguanosine (80HdG) were determined in 33 men occupationally exposed to benzene from gasoline and in 33 controls. The average exposure to benzene over a shift was determined by personal air sampling in the breathing zone. The 8-hr time-weighted average exposure to benzene was 0.13 ppm (mean value, range 0.003–0.6 ppm). Exposed workers had a significant increase of SSB (p = 0.04) over the shift compared with controls. Storage time of the samples seemed to affect the results. An analysis of samples with the same storage time showed a nonsignificant increase among the workers compared with controls. Urinary 80HdG increased over the shift among the exposed workers but not among the controls. The highest values among the exposed workers were seen in late evening, with a slight decrease the next morning. Multiple linear analysis adjusting for smoking habits showed a significant association between the exposure level of benzene during the shift and the increase of 80HdG in the urine over the shift among exposed workers (p = 0.02). These findings indicate a genotoxic effect in humans of benzene at relatively low exposure levels, that is, about 0.1 ppm (0.3 mg/m³). © 1996 Wiley-Liss, Inc.