Effect of exposure to low concentrations of benzene on miR-223 and miR-155 expression in peripheral blood lymphocytes
WANG Aihong1,2, LI Xiaohai1,2, LENG Pengbo1,2, DUAN Donghui1,2, FANG Lanyun1,2, ZHANG Dandan1,2
1. Department of Environmental and Occupational Health, Ningbo Center for Disease Control and Prevention,Ningbo, Zhejiang 315010, China; 2. Zhejiang Provincial Key Laboratory of Health Risk Appraisal for Trace Toxic Chemicals, Ningbo, Zhejiang 315010, China
Abstract:Objective To investigate the effect of exposure to low concentrations of benzene on miR-155 and miR-223 expression in peripheral blood lymphocytes among workers with benzene exposure. Methods A hundred male employees at a risk of exposure to benzene (the exposed group) were randomly sampled from two small metal products manufacturing enterprises and one medium-sized chemical raw material and chemical products manufacturing enterprise in Ningbo City, Zhejiang Province, and 60 age-matched male employees without benzene exposure were randomly selected as the unexposed group. Age, body mass index ( BMI ), smoking status, alcohol consumption, disease history, medication history and routine blood testing results of subjects were collected using a questionnaire survey. The 8-hour time weighted average concentration ( CTWA ) of benzene was measured in the workplace using thermal desorption gas chromatography, and the urine 8-hydroxy-2' deoxyguanosine ( 8-OHdG ) levels were determined using high-performance liquid-chromatography tandem mass spectrometry (HPLC-MS/MS). The miR-155 and miR-223 expression was quantified in peripheral blood lymphocytes using quantitative fluorescent reverse transcription-polymerase chain reaction assay, and the factors affecting miR-155 and miR-223 expression were identified using multivariable logistic regression analysis. Results The subjects in the exposed group had a mean age of ( 31.17±7.30 ) years, and were exposed to low concentrations of benzene ( CTWA, 0.05 to 0.30 mg/m3 ) , while the subjects in the unexposed group had a mean age of ( 32.52±6.15 ) years. There were no significant differences between the exposed and unexposed groups in terms of age, BMI, proportion of smokers or proportion of alcohol consumers ( P>0.05 ). There was no significant difference in the median relative miR-155 expression between the exposed and unexposed groups ( 0.953 vs. 1.293, P>0.05 ), and lower median relative miR-223 expression was quantified in the exposed group than in the unexposed group ( 0.540 vs. 1.433, P<0.05 ). Multivariable logistic regression analysis revealed that down-regulation of miR-223 expression correlated with exposure to benzene ( OR=2.719, 95%CI: 1.308-5.651 ). Conclusion Down-regulation of miR-223 expression may be associated with exposure to low concentrations of benzene.
[1] SCHNATTER A R,KERZIC P J,ZHOU Y,et al.Peripheral blood effectsin benzene-exposed workers[J].Chem Biol Interact,2010,184(1/2):174-181. [2] VIANNA N J,POLAN A.Lymphomas and occupational benzene exposure[J].Lancet,1979,313(8131):1394-1395. [3] 刘洋,张恒东,陈献文,等.苯作业工人血浆差异表达微小RNA的初步筛选与分析[J].中华劳动卫生职业病杂志,2014,32(7):511-515. LIU Y,ZHANG H D,CHEN X W,et al.Screening and analysis of plasma microRNA profile in benzene exposed workers[J].Chin J Ind Hyg Occup Dis,2014,32(7):511-515. [4] BAI W L,CHEN Y J,YANG J,et al.Aberrant miRNA profiles associated with chronic benzene poisoning[J].Exp Mol Pathol,2014,96(3):426-430. [5] 中华人民共和国卫生部.血细胞分析参考区间:WS/T 405—2012[S].2012. Ministry of Health of the People's Republic of China.Reference intervals for blood cell analysis:WS/T 405-2012[S].2012. [6] 中华人民共和国卫生部.工作场所空气中有害物质监测的采样规范:GBZ 159—2004[S].北京:人民卫生出版社,2004. Ministry of Health of the People's Republic of China.Specifications of air sampling for hazardous substances monitoring in the workplace:GBZ 159-2004[S].Beijing:People's Medical Publishing House,2004. [7] 中华人民共和国国家卫生和计划生育委员会.工作场所空气有毒物质测定第66部分:苯、甲苯、二甲苯和乙苯:GBZ/T 300.66—2017[S].2017. National Health and Family Planning Commission of the People's Republic of China.Determination of toxic substances in workplace air-Part 66:benzene,toluene,xylene and ethyl benzene:GBZ/T 300.66-2017[S].2017. [8] 王爱红,李晓海,冷朋波,等.低浓度苯暴露男性工人尿8-OHdG水平的影响因素[J].环境与职业医学,2020,37(3):243-248. WANG A H,LI X H,LENG P B,et al.Influencing factors of urinary 8-OHdG concentration in male workers exposed to low levels of benzene[J].J Environ Occup Med,2020,37(3):243-248. [9] LIVAK K J,SCHMITTGEN T D.Analysis of relative gene expression data using real-time quantitative PCR and the 2-△△Ct method[J].Methods,2001,25:402-408. [10] 朱丹霞,缪扣荣,朱远东,等.实时定量PCR检测白血病相关miRNA方法的建立[J].中国实验血液学杂志,2010,18(3):756-761. ZHU D X,MIAO K R,ZHU Y D,et al.Detection of miRNA levels in leukemia patients by real-time quantitative PCR[J].J Exp Hematol,2010,18(3):756-761. [11] 王秋艳,武志云,张岩,等.低浓度苯及混苯对接触工人血常规及淋巴细胞微核的影响[J].河北医药,2020,42(8):1250-1253. WANG Q Y,WU Z Y,ZHANG Y,et al.Effects of low concentration benzene on blood routine count and lymphocyte micronucleus in exposed workers[J].Hebei Med J,2020,42(8):1250-1253. [12] 彭艳,张磊,朱媛媛,等.杭州市苯接触作业在岗工人血常规异常及影响因素分析[J].预防医学,2020,32(10):1059-1061. PENG Y,ZHANG L,ZHU Y Y,et al.Abnormality in routine blood tests and its influencing factors among workers exposed to benzene in Hangzhou[J].Prev Med,2020,32(10):1059-1061. [13] KIM J H,MOON J Y,PARK E Y,et al.Changes in oxidative stress biomarker and gene expression levels in workers exposed to volatile organic compounds[J].Ind Health,2011,49(1):8-14. [14] LIU Y,CHEN X W,NIAN Q,et al.Analysis of plasma microRNA expression profiles in a Chinese population occupationally exposed to benzene and in a population with chronic benzene poisoning[J].J Thorac Dis,2016,8(3):403-414. [15] WEI H Y,ZHANG J,TAN K H,et al.Benzene-induced aberrant miRNA expression rofile in hematopoietic progenitor cells in C57BL/6 mice[J].Int J Mol Sci,2015,16(11):27058-27071. [16] 叶伟国,黄浩宇,姜燃,等.氢醌处理人支气管上皮细胞(16HBE)对其miR-221及抑癌基因PTENmRNA表达的影响[J].毒理学杂志,2019,33(3):226-229. [17] BISWAS R,MAHESH G.MicroRNA-155:a master regulator of inflammation[J].J Interferon Cytokine Res,2019,39(6):321-330. [18] JOHNNIDIS J B,HARRIS M H,WHEELER R T,et al.Regulation of progenitor cell proliferation and granulocyte function by microRNA-223[J].Nature,2008,451(7182):1125-1129. [19] AOKI H,TANI H,NAKAMURA K,et al.MicroRNA biomarkers for chemical hazard screening identified by RNA deep sequencing analysis in mouse embryonic stem cells[J/OL].Toxicol Appl Pharmacol,2020,392[2021-12-01].https://doi.org/10.1016/j.taap.2020.114929. [20] 王爱红,李晓海,冷朋波.苯毒性作用机制及其与miRNA关系的研究进展[J].中华劳动卫生职业病杂志,2018,36(3):237-240. WANG A H,LI X H,LENG P B.Research progress on toxicity mechanism of benzene and its relationship with miRNA[J].Chin J Ind Hyg Occup Dis,2018,36(3):237-240.