Sisto Renata, Capone Pasquale, Cerini Luigi, Paci Enrico, Pigini Daniela, Gherardi Monica, Gordiani Andrea, L'Episcopo Nunziata, Tranfo Giovanna, Chiarella Pieranna
Italian Workers Compensation Authority (INAIL), Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, via di Fontana Candida 1, 00078, Monte Porzio Catone, Rome, Italy.
Toxicol Rep. 2020 Jun 3;7:700-710. doi: 10.1016/j.toxrep.2020.05.006. eCollection 2020.
In the framework of a project aimed at finding novel predictive biomarkers of VOCs exposure-related diseases, the effect of exposure to ethylbenzene, toluene, and xylene has been analyzed in a group of painters (spray- and roller-painters) working in the shipyard industry. Airborne levels of solvents were higher in spray- than in roller-painters, and comparable to the Occupational Exposure Limits (OELs), particularly for toluene and xylene. The urinary concentration of each volatile organic compound (VOC) and of the corresponding metabolites were also concurrently measured. A set of oxidative stress biomarkers, i.e., the products of DNA and RNA oxidation, RNA methylation, and protein nitration, were measured, and found significantly higher at the end of the work shift. MicroRNA (MiRNA) expression was analyzed in the VOC-exposed workers and in a control group, finding 56 differentially expressed (DE) miRNAs at a statistically significant level (adjusted p ≤ 0.01). The Receiver-Operating Characteristic curves, computed for each identified miRNA, showed high sensitivity and specificity. A pathway analysis in the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that miRNA-1, which was found downregulated in exposed workers, is involved in the lung cancer oncogenesis. A subset of 10 miRNAs (out of the 56 DE) was selected, including those with the highest correlation to the urinary dose biomarkers measured at the end of work-shift. Multivariate ANOVA analysis showed a statistically significant correlation between the urinary dose biomarkers (both the VOCs urinary concentration and the VOCs' metabolite concentration), and the identified miRNA subset, indicating that the exposure to low VOC doses may be sufficient to activate the miRNA response. Four miRNAs belonging to the subset strongly related to the VOCs and VOCs' metabolites concentration were individuated, miR-589-5p, miR-941, miR-146b-3p and miR-27a-3p, with well-known implications in oxidative stress and inflammation processes.
在一个旨在寻找挥发性有机化合物（VOCs）暴露相关疾病新型预测生物标志物的项目框架内，对一组在造船厂行业工作的油漆工（喷漆工和滚涂工）接触乙苯、甲苯和二甲苯的影响进行了分析。喷漆工空气中溶剂水平高于滚涂工，且与职业接触限值（OELs）相当，尤其是甲苯和二甲苯。同时还测量了每种挥发性有机化合物（VOC）及其相应代谢物的尿浓度。测量了一组氧化应激生物标志物，即DNA和RNA氧化产物、RNA甲基化和蛋白质硝化产物，发现其在工作班次结束时显著升高。对VOC暴露工人和对照组进行了微小RNA（MiRNA）表达分析，发现56种差异表达（DE）的MiRNA具有统计学显著水平（校正p≤0.01）。为每个鉴定出的MiRNA计算的受试者工作特征曲线显示出高灵敏度和特异性。京都基因与基因组百科全书（KEGG）中的通路分析表明，在暴露工人中发现下调的MiRNA - 1参与肺癌肿瘤发生。从56种DE MiRNA中选择了10种MiRNA子集，包括与工作班次结束时测量的尿剂量生物标志物相关性最高的那些。多变量方差分析显示尿剂量生物标志物（VOCs尿浓度和VOCs代谢物浓度）与鉴定出的MiRNA子集之间存在统计学显著相关性，表明低剂量VOC暴露可能足以激活MiRNA反应。鉴定出四种与VOCs和VOCs代谢物浓度密切相关的MiRNA子集，即miR - 589 - 5p、miR - 941、miR - 146b - 3p和miR - 27a - 3p，它们在氧化应激和炎症过程中具有众所周知的影响。
