Dry tobacco leaves: an in vivo and in silico approach to the consequences of occupational exposure.

IF 2.5 4区 医学 Q3 GENETICS & HEREDITY Mutagenesis Pub Date : 2023-05-12 DOI:10.1093/mutage/gead003
Daiana Dalberto, Ana L H Garcia, Melissa R De Souza, Juliana Picinini, Solange Soares, Guilherme M S De Souza, Paola Chytry, Johnny F Dias, Mirian Salvador, Fernanda R Da Silva, Juliana Da Silva
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Abstract

Exposure of tobacco workers handling dried tobacco leaves has been linked to an increased risk of toxicity and respiratory illness due to the presence of nicotine and other chemicals. This study aimed to evaluate the DNA damage caused by the exposure of tobacco growers during the dry leaf classification process and the relation to cellular mechanisms. A total of 86 individuals participated in the study, divided into a group exposed to dry tobacco (n = 44) and a control group (n = 42). Genotoxicity was evaluated using the alkaline comet assay and lymphocyte micronucleus (MN) assay (CBMN-Cyt), and measurement of telomere length. The levels of oxidative and nitrosative stress were evaluated through the formation of thiobarbituric acid reactive species, and nitric oxide levels, respectively. The inorganic elements were measured in the samples using particle-induced X-ray emission method. The combination of variables was demonstrated through principal component analysis and the interactions were expanded through systems biology. Comet assay, MN, death cells, thiobarbituric acid reactive species, and nitrosative stress showed a significant increase for all exposed groups in relation to the control. Telomere length showed a significant decrease for exposed women and total exposed group in relation to men and control groups, respectively. Bromine (Br) and rubidium (Rb) in the exposed group presented higher levels than control groups. Correlations between nitrate and apoptosis; Br and MN and necrosis; and Rb and telomeres; besides age and DNA damage and death cells were observed. The systems biology analysis demonstrated that tobacco elements can increase the nuclear translocation of NFKB dimers inducing HDAC2 expression, which, associated with BRCA1 protein, can potentially repress transcription of genes that promote DNA repair. Dry tobacco workers exposed to dry leaves and their different agents showed DNA damage by different mechanisms, including redox imbalance.

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干烟叶:用体内和硅学方法研究职业接触的后果。
由于烟草中含有尼古丁和其他化学物质,处理干烟叶的烟草工人接触烟草会增加中毒和呼吸道疾病的风险。本研究旨在评估烟草种植者在干叶分级过程中接触烟叶造成的 DNA 损伤及其与细胞机制的关系。共有 86 人参与了这项研究,分为接触干烟叶组(44 人)和对照组(42 人)。使用碱性彗星试验和淋巴细胞微核(MN)试验(CBMN-Cyt)以及端粒长度测量来评估遗传毒性。氧化应激和亚硝酸应激水平分别通过硫代巴比妥酸活性物质的形成和一氧化氮水平进行评估。利用粒子诱导 X 射线发射法测量了样本中的无机元素。通过主成分分析证明了变量的组合,并通过系统生物学扩展了变量之间的相互作用。与对照组相比,所有暴露组的彗星试验、MN、死亡细胞、硫代巴比妥酸活性物质和亚硝基应激均显著增加。与男性和对照组相比,暴露妇女和总暴露组的端粒长度分别明显下降。暴露组的溴和铷含量高于对照组。除了年龄与 DNA 损伤和死亡细胞之间的关系外,还观察到硝酸盐与细胞凋亡、Br 与 MN 和坏死、Rb 与端粒之间的关系。系统生物学分析表明,烟草元素可增加 NFKB 二聚体的核转位,诱导 HDAC2 的表达,而 HDAC2 与 BRCA1 蛋白相关,可能会抑制促进 DNA 修复的基因转录。暴露于旱烟叶及其不同药剂的旱烟工人通过不同的机制(包括氧化还原失衡)出现DNA损伤。
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来源期刊
Mutagenesis
Mutagenesis 生物-毒理学
CiteScore
5.90
自引率
3.70%
发文量
22
审稿时长
6-12 weeks
期刊介绍: Mutagenesis is an international multi-disciplinary journal designed to bring together research aimed at the identification, characterization and elucidation of the mechanisms of action of physical, chemical and biological agents capable of producing genetic change in living organisms and the study of the consequences of such changes.
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