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职业暴露于环氧乙烷的医院护士的遗传毒理学调查:I.外周血淋巴细胞中的染色体畸变、姐妹染色单体交换、细胞周期动力学及紫外线诱导的DNA合成

Genotoxicological investigation of hospital nurses occupationally exposed to ethylene-oxide: I. Chromosome aberrations, sister-chromatid exchanges, cell cycle kinetics, and UV-induced DNA synthesis in peripheral blood lymphocytes.

作者信息

Major J, Jakab M G, Tompa A

机构信息

National Institute of Occupational Health, Department of Genotoxicology, Budapest, Hungary.

出版信息

Environ Mol Mutagen. 1996;27(2):84-92. doi: 10.1002/(SICI)1098-2280(1996)27:2<84::AID-EM2>3.0.CO;2-E.

Abstract

Structural, and numeric chromosome aberrations (CA), sister-chromatid exchange (SCE), phytohemagglutinin stimulation (LI), proliferative rate index (PRI), and UV light-induced unscheduled DNA-synthesis (UDS) were investigated in peripheral blood lymphocytes (PBL) of 48 historical controls ("Controls"); of 14 hospital controls in Budapest, Hungary ("Budapest controls"); of 9 nurses occupationally exposed to low-dose ethylene-oxide in Budapest ("Budapest exposed"); of 10 hospital controls in Eger, Hungary ("Eger controls"); and of 27 high dose ETO-exposed nurses in Eger ("Eger exposed"), where neoplasias, mainly breast cancers, were observed. ETO concentrations in the ambient air samples varied from 5 to 20 mg/m3 in Budapest; and from 5 to 100 mg/m3 in Eger. Bothe LI and PRI were depressed in Budapest exposed, indicating ETO-induced cytotoxicity and, however, normal in Eger exposed. SCE was slightly elevated in Budapest exposed, but significantly increased in Eger exposed. The yields of cells with high frequency SCE (HFC) were only increased in Eger exposed. The expected low CA frequencies were found in Controls and in Budapest controls. ETO exposures significantly increased the CA frequencies in Budapest and Eger exposed. In Budapest exposed, as expected, we found deletions; in a lesser extent chromatid exchanges and dicentrics; but no rings were detected. These results are in a good accordance to the published data of other investigations carried out on ETO-exposed human populations. However, in Eger exposed, beside the increased yields of deletions, the frequencies of dicentrics and rings showed a significant excess compared to the reviewed data. An unexpected, significant increase of dicentric and ring frequencies was also detected among the hospital controls in Eger controls without known clastogenic exposure. The role of confounding factors (age, smoking and drinking habit, total leukocyte count and hematocrit) was investigated by an analysis of variance on CA and SCE frequencies in Controls and in Eger exposed. Leukocyte count and mean age showed only significant effects on CA in Eger exposed and on SCE in Controls, respectively. A possible active confounding factor could be the temporary natural radioactivity of the local tap water. UDS in Budapest exposed and in Eger control were significantly higher then in the Controls and in Budapest controls. In Eger exposed UDS was significantly decreased compared to the Budapest exposed and Eger control groups. The explanation of the present results is difficult on the basis of the reviewed data on ETO-induced CA frequencies in exposed human populations, and it raises an issue of an independent genotoxic effect in Eger, which is common both in Eger controls and in Eger exposed, such as natural radioactivity.

摘要

对48名历史对照者(“对照组”)、匈牙利布达佩斯的14名医院对照者(“布达佩斯对照者”)、布达佩斯9名职业性接触低剂量环氧乙烷的护士(“布达佩斯接触者”)、匈牙利埃格尔的10名医院对照者(“埃格尔对照者”)以及埃格尔27名高剂量环氧乙烷接触护士(“埃格尔接触者”)的外周血淋巴细胞(PBL)进行了结构和数量染色体畸变(CA)、姐妹染色单体交换(SCE)、植物血凝素刺激(LI)、增殖率指数(PRI)以及紫外线诱导的非预定DNA合成(UDS)的研究,在埃格尔观察到了肿瘤,主要是乳腺癌。布达佩斯环境空气样本中的环氧乙烷浓度在5至20毫克/立方米之间;埃格尔的浓度在5至100毫克/立方米之间。布达佩斯接触者的LI和PRI均降低,表明环氧乙烷诱导了细胞毒性,然而,埃格尔接触者的LI和PRI正常。布达佩斯接触者的SCE略有升高,但埃格尔接触者的SCE显著增加。高频SCE(HFC)细胞的产率仅在埃格尔接触者中增加。对照组和布达佩斯对照者中发现预期的低CA频率。环氧乙烷暴露显著增加了布达佩斯和埃格尔接触者的CA频率。在布达佩斯接触者中,如预期的那样,发现了缺失;在较小程度上有染色单体交换和双着丝粒;但未检测到环状染色体。这些结果与其他关于环氧乙烷接触人群的研究发表的数据非常一致。然而,在埃格尔接触者中,除了缺失产率增加外,双着丝粒和环状染色体的频率与综述数据相比显著过高。在埃格尔对照者中无已知致断裂物暴露的医院对照者中也检测到双着丝粒和环状染色体频率意外显著增加。通过对对照组和埃格尔接触者的CA和SCE频率进行方差分析,研究了混杂因素(年龄、吸烟和饮酒习惯、白细胞总数和血细胞比容)的作用。白细胞计数和平均年龄分别仅对埃格尔接触者的CA和对照组的SCE有显著影响。一个可能的主动混杂因素可能是当地自来水的暂时天然放射性。布达佩斯接触者和埃格尔对照者的UDS显著高于对照组和布达佩斯对照者。与布达佩斯接触者和埃格尔对照组相比,埃格尔接触者的UDS显著降低。根据关于环氧乙烷暴露人群中环氧乙烷诱导的CA频率的综述数据,很难解释目前的结果,这提出了一个关于埃格尔存在独立遗传毒性效应的问题,这种效应在埃格尔对照者和埃格尔接触者中都很常见,比如天然放射性。

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