DNA加合物检测方法研究进展

DNA加合物的研究已成为现代毒理学领域的热点,其检测方法也不断改进、发展,其中包括32p后标记法、免疫学方法、荧光测定法、气谱-质谱法以及一些其他方法.每种方法都存在着一些优势和不足,该文就对其中几种常用的检测方法进行介绍和评述.     

DNA加合物检测方法的研究进展

ＤＮＡ加合物的广泛研究主要是益于近年来研究方法的迅速发展，其中＾３２Ｐ后标记方法，免疫测试法，荧光测定法，气－质谱法，高效液相色谱法以及电化学垢引入起了重要的作用，本文对其中几种常用的检测法及其进展进行综述。     

有关苯DNA加合物的研究进展

苯是一种广泛用于工业生产的有机溶剂和有机合成的原料。苯对工人的危害可表现为白细胞及血小板减少,严重者可产生再障及白血病等。另外,苯尚与人体及动物体实质性肿瘤、淋巴瘤的发生有关。 近年来,随着分子生物学的迅速发展,人们开始应用分子生物学的方法和理论来探讨苯中毒的机理。随着研究的逐步深入,特别是化学物——DNA加合物分析方法的问世和完善,有关苯及其代谢产物与DNA共价结合的文章也日趋增多。一种理论认为,苯的毒作用可能和苯及其代谢产物与DNA等大分子共价结合形成加合物有关,但由于方法本身建立不久,有关苯或其代谢产物DNA加合物的研究尚很初步。本文则拟从苯及其代谢产物DNA加合物的形成及结构分析、加合物的持续     

苯—DNA加合物结构研究进展

苯－ＤＮＡ加合物结构研究进展王登忠综述李桂兰尹松年邹昌淇审校苯及其代谢产物可与ＤＮＡ分子上的碱基共价结合，形成加合物，通称为苯－ＤＮＡ加合物。苯－ＤＮＡ加合物的结构研究对揭示苯的致癌机制具有重要意义。近十年来，随着小分子量芳香族化学物－ＤＮＡ加合物后...     

DNA加合物检测方法研究进展

每年,人类都将新合成数以千计的化学物质用于生产、生活,并最终排放到环境当中,其中,许多化学物质可能具有遗传毒性。如何对这些物质进行监测和评价是一项十分艰难而重要的工作。随着研究的深入,人们提出应用大分子(蛋白质、RNA、DNA)加合物来研究其遗传毒性,其中DNA加合物由于意义重大而成为多学科的研究热点。DNA加合物就是亲电性的化学物质或其代谢产物与生物体内的DNA共价相连形成的复合体,是DNA化学损伤最重要和最普遍的形式。DNA加合物形成后,一旦逃避了自身的修复,就可能成为致突变、致畸、致癌的启动因子。所以,DNA加合物既可以作为接触标志物,反映毒物在靶部位的效应剂量,又可以作为效应标志物,反映DNA的损伤程度。     

重量法测定血苯-白蛋白加合物的初步研究

苯进入人体内形成有很高活性的环氧化物，可与多种蛋白形成加合物。有研究用同位素标记的苯（Ｃ６２Ｈ６）白蛋白为内标衍生后，用气质联仪（ＧＣＭＳ）测定血液中的苯白蛋白加合物［１］。由于采用昂贵的仪器和同位素内标物，在一般实验室难以进行。本研究采用重...     

苯代谢产物DNA加合物形成特性研究

苯代谢产物ＤＮＡ加合物形成特性研究王春光，李桂兰，尹松年苯是一种广泛用于工业生产的有机溶剂和有机合成的原料，它能影响骨髓的造血功能引起慢性苯中毒，并与白血病的发病有关。近年来，一种理论认为，苯的毒作用可能和苯及其代谢产物与ＤＮＡ等大分子共价结合形成加...     

苯—DNA加合物类型与化学特性

本就苯及其代谢产物与ＤＮＡ形成的加合物类型的判定方法以及不同类型苯－ＤＮＡ加合物的化学特性做一述评。     

职业接触环氧丙烷工人Hb加合物及其遗传毒性分析

目的 研究长期接触低浓度环氧丙烷工人的遗传效应。方法 采用气相色谱法对环氧丙烷作业现场进行监测的同时,采集工人血样,采用高灵敏的N-alkyl Edman气质谱法对血红蛋白加合物(HP-缬氨酸)含量进行了测定,同时对姐妹染色单体互换(SCE)进行检测。结果 环氧丙烷作业工人时间加权平均浓度(TWA)为2．6mg/m^3和6．9mg／m^3。环氧丙烷接触组工人的HP-缬氨酸水平明显高于对照组,差异有极显著性(P=0．0018)。接触组中的每个细胞SCE数明显高于对照组,差异有显著性(P=0．011)。血红蛋白加合物与姐妹染色单体互换的相关系数r为0．762．并且差异有极显著性(P=0．0014)。结论 低浓度环氧丙烷对职业人群具有细胞遗传学毒性。     

苯接触的易感性生物标志物研究进展

苯是工业生产中重要的生产原料和有机溶剂,油漆、制鞋、制药等行业都使用苯。苯的长期接触可引起白细胞减少、骨髓抑制,严重时可致白血病。但在同一工作环境中,并非所有工人都发生苯中毒,即个体对苯毒性的易感性存在差异,这种易感性差异主要是由基因的多态性造成的。基因的多态性是生物进化早期基因突变造成的,能稳定遗传,可改变基因的表达水平和基因功能,与疾病相关。因此确定敏感的、特异的易感性生物标志物对预防和控制苯中毒、保护接触苯人群的健康具有重要意义。苯中毒易感性生物标志物的研究较多,本文着重从苯代谢酶基因多态性、细胞…     

苯接触人群的生物标志物研究进展

苯是应用广泛的化工原料.接触苯可引起急、慢性苯中毒,甚至白血病.研究苯接触人群的生物标志物在了解苯致病机制、接触苯人群的健康筛查等方面有重要价值,下面就国内外关于苯接触人群的生物标志物的研究进行综述. 1 苯的接触标志物 接触标志物是指进入机体内的外源性物质、代谢产物和它们与靶分子交互作用的产物.苯进入人体后多储留在脂肪组织内,在肝脏氧化成苯环氧化物,环氧化物与谷胱甘肽结合,形成苯巯基尿酸(S-PMA),其半减期为12.8 h[1].PACI等[2]利用高效液相色谱-串联质谱联用(HPLC/MS/MS)对S-PMA进行了研究,得到了尿S-PMA与苯的时间加权平均浓度直线相关,且不受性别、年龄、吸烟习惯的影响.     

Biomonitoring of exposure to ethylene oxide and propylene oxide by determination of hemoglobin adducts: correlations between airborne exposure and adduct levels

Objectives: Ethylene oxide (EO) and propylene oxide (PO) are important industrial chemicals. Exposure to these directly acting mutagens may be monitored by determination of their adducts to hemoglobin (Hb). This study establishes correlations between airborne concentrations of EO and PO and their Hb adducts in petrochemical workers. Methods: In three different studies conducted during maintenance shutdown of petrochemical plants the external occupational exposure to EO and PO was assessed by personal air monitoring (PAM). The internal exposure to EO and PO was concomitantly assessed by determination of N-(2-hydroxyethyl)valine (HOEtVal) and N-(3-hydroxypropyl)valine (HOPrVal) in blood samples of the operators using the N-alkyl-Edman degradation method. Results: In the first study, PAM was applied once a month at random over a period of 4 months. Blood samples for Hb-adduct determination were collected at the end of this period. No significant correlation was found between PAM and Hb-adduct data. In the next two studies, PAM was applied to the operators during the entire shift on every working day during the shutdown. Blood samples were collected before and immediately after the shutdown period. Highly significant correlations were found between the increment in the concentration of HOEtVal and HOPrVal over this period and the total exposure to EO and PO, respectively. Conclusions: Time-integrated exposure to EO or PO can be readily and reliably assessed by measurement of the concentration of HOEtVal or HOPrVal in a small blood sample. In workers occupationally exposed to low concentrations of EO or PO, good correlations were found between these Hb adducts and the airborne concentrations of EO and PO. These correlations allow the calculation of tentative biological exposure limits (BELs) for EO and PO. At the current Dutch occupational exposure limit (OEL) for EO (0.84 mg m⁻³, 8-h TWA) the BEL is 3.2 nmol HOEtVal/g globin. At the value of 10 mg m⁻³ (8-h TWA), which is currently being investigated as the new Dutch OEL for PO, the corresponding BEL is 5.3 nmol HOPrVal/g globin. Received: 28 July 1998 / Accepted: 28 November 1998     

急性环氧乙烷中毒研究进展

环氧乙烷(Ethylene oxide,CAS No.9003-56-9),分子式(CH2)2O,别名氧化乙烯、1,2-环氧乙烷、恶烷,工业上主要用作溶剂、增效剂及高能原料,常作为合成乙二醇等的化工原料.     

流行性感冒病毒检测方法的研究进展

近几年,流行性感冒（流感）在全球范围频繁暴发,2009年暴发了甲型流感（甲流）,2013年又暴发了H7N9的禽流感疫情,势必会威胁着动物和人类的生存和社会的经济的发展,从而使医学工作者关注的焦点转移到流感病毒的鉴定上,所以建立快速、高效的流感病毒检测方法,对于流感患者的临床诊断、有效及时的治疗有着非常重大的意义。作者综述了国内外流感病毒的检测方法,主要有血清免疫学检测、流感病毒分离培养、流感病毒核酸检测、环介导等温扩增法、基因芯片技术等。但每一种方法都有一定的优点和不足。随着科学技术水平的提高,更多的方法将应用到流感病毒检测中,同时方法间的互相融合更加提升了现有的检测水平,从而一定会在流感的监测、控制和预防工作中发挥更为积极有效的作用。     

三硝基甲苯血红蛋白加合物与接触量的关系

目的：探讨反映三硝基甲苯（TNT）接触水平的生物标志物，研究TNT作业工人体内的血红蛋白加合物与接触量的关系。方法：使用GC－MS法测定25名TNT作业工人血液中TNT血红蛋白加合物（4A－Hb、2A－Hb）的含量，观察其与接触量的相关性。接触水平以空气污染量和皮肤污染量表示。结果：血红蛋白加合物4A－Hb、2A－Hb与总接触水平相关，尤其与皮肤接触量相关性更强；其中4A－Hb与总接触水平的回归曲线和血红蛋白加合物总量（4A－Hb 2A-Hb)与总接触水平的回归曲线的斜率（F＝0．03）及截距（F＝0．11）的差异均无显著性（P＞0．05）。结论：血红蛋白加合物4A-Hb、2A－Hb均可用于评价TNT总接触水平，其中4A－Hb更适宜评价TNT的接触水平。     

一氧化氮在微生物感染中的双向作用

1992年，一氧化氮（Nitric Oxide，NO）被《Science》杂志评为年度明星分子，对NO的生物学作用研究已经成为一个非常热门的课题。早期的研究表明，NO在促进血液循环、预防动脉硬化、恢复血管弹性、降低血压、加强心脏功能，甚至在治疗糖尿病、脑卒中、老年痴呆、性功能障碍等方面都有明显作用。最近的研究发现其在微生物感染中也具有独特的作用。     

苯的溶剂解吸型活性炭管盲样检测方法探讨

目的探讨溶剂解吸型活性炭管检测苯的方法;探讨溶剂解吸型活性炭管苯解吸效率的测定方法。方法用苯的溶剂解吸气相色谱法;用活性炭管吸附苯标准溶液,然后经二硫化碳解吸,振摇1 min,解吸30 min,在给定的色谱条件下分析。结果本次盲样检测结果为39.93μg,合格。结论通过测定计算活性炭管的解吸率,来进行苯的溶剂解吸-气相色谱法盲样检测,结果准确性高,方法可靠,并适用于基层单位的检测工作。     

Albumin adducts of electrophilic benzene metabolites in benzene-exposed and control workers

BACKGROUND: Metabolism of benzene produces reactive electrophiles, including benzene oxide (BO), 1,4-benzoquinone (1,4-BQ), and 1,2-benzoquinone (1,2-BQ), that are capable of reacting with blood proteins to produce adducts. OBJECTIVES: The main purpose of this study was to characterize relationships between levels of albumin adducts of these electrophiles in blood and the corresponding benzene exposures in benzene-exposed and control workers, after adjusting for important covariates. Because second blood samples were obtained from a subset of exposed workers, we also desired to estimate within-person and between-person variance components for the three adducts. METHODS: We measured albumin adducts and benzene exposures in 250 benzene-exposed workers (exposure range, 0.26-54.5 ppm) and 140 control workers (exposure range < 0.01-0.53 ppm) from Tianjin, China. Separate multiple linear regression models were fitted to the logged adduct levels for workers exposed to benzene < 1 ppm and > or =1 ppm. Mixed-effects models were used to estimate within-person and between-person variance components of adduct levels. RESULTS: We observed nonlinear (hockey-stick shaped) exposure-adduct relationships in log-scale, with inflection points between about 0.5 and 5 ppm. These inflection points represent air concentrations at which benzene contributed marginally to background adducts derived from smoking and from dietary and endogenous sources. Adduct levels were significantly affected by the blood-collection medium (serum or plasma containing either heparin or EDTA), smoking, age, and body mass index. When model predictions of adduct levels were plotted versus benzene exposure > or =1 ppm, we observed marked downward concavity, particularly for adducts of the benzoquinones. The between-person variance component of adduct levels increased in the order 1,2-BQ < 1,4-BQ < BO, whereas the within-person variance components of the three adducts followed the reverse order. CONCLUSIONS: Although albumin adducts of BO and the benzoquinones reflect exposures to benzene > or = 1 ppm, they would not be useful biomarkers of exposure at ambient levels of benzene, which tend to be < 0.01 ppm, or in those working populations where exposures are consistently < 1 ppm. The concavity of exposure-adduct relationships is consistent with saturable metabolism of benzene at air concentrations > 1 ppm. The surprisingly large effect of the blood-collection medium on adduct levels, particularly those of the benzoquinones, should be further investigated.