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职业性铅和镉暴露的遗传毒性效应。

Genotoxic effects of occupational exposure to lead and cadmium.

作者信息

Palus J, Rydzynski K, Dziubaltowska E, Wyszynska K, Natarajan A T, Nilsson R

机构信息

Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz, Poland.

出版信息

Mutat Res. 2003 Sep 9;540(1):19-28. doi: 10.1016/s1383-5718(03)00167-0.

Abstract

This study was designed to assess genotoxic damage in somatic cells of workers in a Polish battery plant after high-level occupational exposure to lead (Pb) and cadmium (Cd), by use of the following techniques: the micronucleus (MN) assay, combined with in situ fluorescence hybridization (FISH) with pan-centromeric probes, analysis of sister chromatid exchanges (SCEs), and the comet assay. Blood samples from 44 workers exposed to lead, 22 exposed to cadmium, and 52 unexposed persons were used for SCE and MN analysis with 5'-bromodeoxyuridine (BrdU) or cytokinesis block, respectively. In parallel, the comet assay was performed with blood samples from the same persons for detection of DNA damage, including single-strand breaks (SSB) and alkali-labile sites (ALS). In workers exposed mostly to lead, blood Pb concentrations ranged from 282 to 655 microg/l, while the range in the controls was from 17 to 180 microg/l. Cd concentration in lead-exposed workers fell in the same range as for the controls. In workers exposed mainly to cadmium, blood Cd levels varied from 5.4 to 30.8 microg/l, with respective values for controls within the range of 0.2-5.7 microg/l. Pb concentrations were similar as for the controls. The incidence of MN in peripheral lymphocytes from workers exposed to Pb and Cd was over twice as high as in the controls (P<0.01). Using a combination of conventional scoring of MN and FISH with pan-centromeric probes, we assessed that this increase may have been due to clastogenic as well as aneugenic effects. In Cd- and Pb-exposed workers, the frequency of SCEs as well as the incidence of leukocytes with DNA fragmentation in lymphocytes were slightly, but significantly increased ( P<0.05) as compared with controls. After a 3h incubation of the cells to allow for DNA repair, a clear decrease was found in the level of DNA damage in the controls as well as in the exposed workers. No significant influence of smoking on genotoxic damage could be detected in metal-exposed cohorts. Our findings indicate that lead and cadmium induce clastogenic as well as aneugenic effects in peripheral lymphocytes, indicating a potential health risk for working populations with significant exposures to these heavy metals.

摘要

本研究旨在通过以下技术评估波兰一家电池厂工人在高水平职业接触铅(Pb)和镉(Cd)后体细胞中的遗传毒性损伤:微核(MN)试验,结合使用全着丝粒探针的原位荧光杂交(FISH)、姐妹染色单体交换(SCE)分析和彗星试验。分别使用来自44名铅接触工人、22名镉接触工人和52名未接触者的血样,通过5'-溴脱氧尿苷(BrdU)或胞质分裂阻滞法进行SCE和MN分析。同时,对同一批人员的血样进行彗星试验,以检测DNA损伤,包括单链断裂(SSB)和碱不稳定位点(ALS)。在主要接触铅的工人中,血铅浓度范围为282至655微克/升,而对照组的范围为17至180微克/升。铅接触工人中的镉浓度与对照组处于同一范围。在主要接触镉的工人中,血镉水平在5.4至30.8微克/升之间变化,对照组的相应值在0.2至5.7微克/升范围内。铅浓度与对照组相似。接触铅和镉的工人外周淋巴细胞中的微核发生率是对照组的两倍多(P<0.01)。通过将传统的微核评分与使用全着丝粒探针的FISH相结合,我们评估这种增加可能是由于致断裂效应以及非整倍体效应。与对照组相比,接触镉和铅的工人中SCE的频率以及淋巴细胞中DNA片段化白细胞的发生率略有但显著增加(P<0.05)。在细胞孵育3小时以进行DNA修复后,发现对照组以及接触工人的DNA损伤水平明显降低。在金属接触人群中未检测到吸烟对遗传毒性损伤有显著影响。我们的研究结果表明,铅和镉在外周淋巴细胞中诱导致断裂效应以及非整倍体效应,表明大量接触这些重金属的工作人群存在潜在的健康风险。

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