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对职业性接触可能致癌物的受试者的基因组损伤评估。

Evaluation of genome damage in subjects occupationally exposed to possible carcinogens.

作者信息

Zeljezic Davor, Mladinic Marin, Kopjar Nevenka, Radulovic Azra Hursidic

机构信息

Division for Mutagenesis, Institute for Medical Research and Occupational Health, Zagreb, Croatia.

Division for Mutagenesis, Institute for Medical Research and Occupational Health, Zagreb, Croatia

出版信息

Toxicol Ind Health. 2016 Sep;32(9):1570-80. doi: 10.1177/0748233714568478. Epub 2015 Feb 4.

Abstract

In occupational exposures, populations are simultaneously exposed to a mixture of chemicals. We aimed to evaluate DNA damage due to possible carcinogen exposure (phenylhydrazine, ethylene oxide, dichloromethane, and 1,2-dichloroethane) in lymphocytes of pharmaceutical industry workers from the same production line. Population comprised 16 subjects (9 females and 7 males) who were exposed to multiple chemicals for 8 months. Genome damage was assessed using alkaline comet assay, micronucleus assay, and comet assay coupled with fluorescent in situ hybridization (comet-FISH). After 8 months of exposure, the issue of irregular use of all available personal protective equipment (PPE) came into light. To decrease the risk of exposure, strict use of PPE was enforced. After 8 months of strict PPE use, micronuclei frequency and comet assay parameters in lymphocytes of pharmaceutical workers significantly decreased compared with prior period of irregular PPE use. Comet-FISH results indicated a significant shift in distribution of signals for the TP 53 gene toward a more frequent occurrence in the comet tail. Prolonged exposure to possible carcinogens may hinder DNA repair mechanisms and affect structural integrity of TP 53 Two indicators of loss of TP 53 gene integrity have risen, namely, TP 53 fragmentation rate in lymphocytes with persistently elevated primary damage and incidence of TP 53 deletions in undamaged lymphocytes.

摘要

在职业暴露中,人群会同时接触到多种化学物质的混合物。我们旨在评估同一生产线的制药行业工人淋巴细胞中因可能接触致癌物(苯肼、环氧乙烷、二氯甲烷和1,2 - 二氯乙烷)而导致的DNA损伤。研究人群包括16名受试者(9名女性和7名男性),他们接触多种化学物质达8个月之久。使用碱性彗星试验、微核试验以及彗星试验结合荧光原位杂交技术(彗星 - FISH)评估基因组损伤。暴露8个月后,发现存在所有可用个人防护装备(PPE)使用不规范的问题。为降低暴露风险,强制要求严格使用PPE。在严格使用PPE 8个月后,与之前PPE使用不规范时期相比,制药工人淋巴细胞中的微核频率和彗星试验参数显著降低。彗星 - FISH结果表明,TP 53基因信号的分布显著向彗星尾部更频繁出现的方向偏移。长期接触可能的致癌物可能会阻碍DNA修复机制并影响TP 53的结构完整性。TP 53基因完整性丧失的两个指标有所上升,即原发性损伤持续升高的淋巴细胞中TP 53的断裂率以及未受损淋巴细胞中TP 53缺失的发生率。

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