title: Urinary microRNAs as potential biomarkers of pesticide exposure.
abstract: 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 farmworker 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.
authors.affiliation: Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, WA, United States; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States.
authors.forename: Brittany A
authors.initials: BA
authors.lastname: Weldon
authors.affiliation: Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, WA, United States; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States.
authors.forename: Sara Pacheco
authors.initials: SP
authors.lastname: Shubin
authors.affiliation: Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, WA, United States; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States.
authors.forename: Marissa N
authors.initials: MN
authors.lastname: Smith
authors.affiliation: Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, WA, United States; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Workman
authors.affiliation: Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, WA, United States; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States.
authors.forename: Alexander
authors.initials: A
authors.lastname: Artemenko
authors.affiliation: Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, WA, United States; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States.
authors.forename: William C
authors.initials: WC
authors.lastname: Griffith
authors.affiliation: Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
authors.forename: Beti
authors.initials: B
authors.lastname: Thompson
authors.affiliation: Institute for Risk Analysis and Risk Communication, University of Washington, Seattle, WA, United States; Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, United States. Electronic address: faustman@uw.edu.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Faustman
mesh_terms: D015415:Biomarkers / Q000652:urine*; D016000:Cluster Analysis; D004781:Environmental Exposure; D006801:Humans; D057230:Limit of Detection; D035683:MicroRNAs / Q000652:urine*; D010575:Pesticides / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D010575:Pesticides
keywords: Exposure biomarkers; MicroRNA; Organophosphate; Pesticides
references.citation: Cancer Res. 2006 Nov 15;66(22):10843-8
references.pmid: 17108120
references.citation: Environ Health Perspect. 2011 Aug;119(8):A328-9
references.pmid: 21807587
references.citation: J Expo Sci Environ Epidemiol. 2014 Sep-Oct;24(5):522-31
references.pmid: 24594649
references.citation: FEBS Lett. 2005 Oct 31;579(26):5911-22
references.pmid: 16111679
references.citation: Crit Rev Toxicol. 2008;38 Suppl 2:1-125
references.pmid: 18726789
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Mol Cell. 2007 Jul 6;27(1):91-105
references.pmid: 17612493
references.citation: Toxicol Sci. 2004 Jul;80(1):193-202
references.pmid: 15084756
references.citation: Urol Oncol. 2010 Nov-Dec;28(6):655-61
references.pmid: 19375957
references.citation: PLoS One. 2012;7(4):e35345
references.pmid: 22532850
references.citation: J Expo Anal Environ Epidemiol. 2005 Sep;15(5):388-97
references.pmid: 15602583
references.citation: Hum Mol Genet. 2012 Oct 15;21(R1):R125-34
references.pmid: 22872698
references.citation: Nat Genet. 2005 May;37(5):495-500
references.pmid: 15806104
references.citation: Database (Oxford). 2009;2009:bap008
references.pmid: 20157481
references.citation: Eur Urol. 2011 May;59(5):671-81
references.pmid: 21296484
references.citation: Stat Med. 2001 Oct 15;20(19):2921-33
references.pmid: 11568949
references.citation: Toxicol Sci. 2014 Mar;138(1):36-46
references.pmid: 24304932
references.citation: J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Oct 1;878(27):2567-74
references.pmid: 20494630
references.citation: Environ Res. 2011 Aug;111(6):751-6
references.pmid: 21636082
references.citation: Biomarkers. 2015;20(5):299-305
references.pmid: 26329526
references.citation: Environ Health Perspect. 2015 May;123(5):399-411
references.pmid: 25616258
references.citation: Toxicology. 2014 Oct 3;324:158-68
references.pmid: 24863737
references.citation: Clin Chem. 2010 Nov;56(11):1733-41
references.pmid: 20847327
references.citation: Biomark Med. 2013 Aug;7(4):623-31
references.pmid: 23905899
references.citation: Toxicol Sci. 2012 Feb;125(2):335-44
references.pmid: 22112502
references.citation: Science. 2007 Dec 21;318(5858):1931-4
references.pmid: 18048652
references.citation: Comput Methods Programs Biomed. 2004 Jun;74(3):255-60
references.pmid: 15135576
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 17;106(11):4402-7
references.pmid: 19246379
references.citation: Drug Metab Rev. 2015 Aug;47(3):320-34
references.pmid: 26300547
references.citation: Toxicol Appl Pharmacol. 2013 Oct 1;272(1):154-60
references.pmid: 23726802
references.citation: Environ Health Perspect. 1999 Jun;107 Suppl 3:409-19
references.pmid: 10346990
references.citation: Genome Biol. 2003;5(1):R1
references.pmid: 14709173
references.citation: Environ Health Perspect. 2004 Feb;112(2):186-200
references.pmid: 14754573
references.citation: Pharm Res. 2014 Mar;31(3):780-94
references.pmid: 24078287
references.citation: Development. 2005 Nov;132(21):4653-62
references.pmid: 16224045
references.citation: Toxicol Appl Pharmacol. 2015 Apr 15;284(2):180-7
references.pmid: 25708609