Urinary microRNAs as potential biomarkers of pesticide exposure

被引:28
作者
Weldon, Brittany A. [1 ,2 ]
Shubin, Sara Pacheco [1 ,2 ]
Smith, Marissa N. [1 ,2 ]
Workman, Tomomi [1 ,2 ]
Artemenko, Alexander [1 ,2 ]
Griffith, William C. [1 ,2 ]
Thompson, Beti [3 ]
Faustman, Elaine M. [1 ,2 ]
机构
[1] Univ Washington, Inst Risk Anal & Risk Commun, Seattle, WA 98195 USA
[2] Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA
[3] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA
基金
美国国家卫生研究院; 美国国家环境保护局;
关键词
MicroRNA; Organophosphate; Pesticides; Exposure biomarkers; ANIMAL DEVELOPMENT; CHILDREN; VARIABILITY; EXPRESSION; IDENTIFICATION; DETERMINANTS; SPECIFICITY; METABOLITES; PROFILES; INJURY;
D O I
10.1016/j.taap.2016.01.018
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
MicroRNAs (miRNAs) are post-transcriptional regulators that silence messenger RNAs. Because miRNAs are stable at room temperature and long-lived, they have been proposed as molecular biomarkers to monitor disease and exposure status. While urinary miRNAs have been used clinically as potential diagnostic markers for kidney and bladder cancers and other diseases, their utility in non-clinical settings has yet to be fully developed. Our goal was to investigate the potential for urinary miRNAs to act as biomarkers of pesticide exposure and early biological response by identifying the miRNAs present in urine from 27 parent/child, farmworker/non-farmworker pairs (16FW/11NFW) collected during two agricultural seasons (thinning and post-harvest) and characterizing the between- and within-individual variability of these miRNA epigenetic regulators. MiRNAs were isolated from archived urine samples and identified using PCR arrays. Comparisons were made between age, households, season, and occupation. Of 384 miRNAs investigated, 297 (77%) were detectable in at least one sample. Seven miRNAs were detected in at least 50% of the samples, and one miRNA was present in 96% of the samples. Principal components and hierarchical clustering analyses indicate significant differences in miRNA profiles between farm worker and non-farmworker adults as well as between seasons. Six miRNAs were observed to be positively associated with farmworkers status during the post-harvest season. Expression of five of these miRNA trended towards a positive dose response relationship with organophosphate pesticide metabolites in farmworkers. These results suggest that miRNAs may be novel biomarkers of pesticide exposure and early biological response. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码:19 / 25
页数:7
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