DNA methylation modifies urine biomarker levels in 1,6-hexamethylene diisocyanate exposed workers: a pilot study

Details

• Personal Author:
  Boyer JC ; French JE ; Fry RC ; Nylander-French LA ; Sanders AP ; Smeester L ; Wu MC
• Description:
  DNA methylation may mediate inter-individual responses to chemical exposure and, thus, modify biomarker levels of exposure and effects. We analyzed inter-individual differences in inhalation and skin exposure to 1,6-hexamethylene diisocyanate (HDI) and urine biomarker 1,6-hexamethylene diamine (HDA) levels in 20 automotive spray-painters. Genome-wide 5-methyl cytosine (CpG) DNA methylation was assessed in each individual's peripheral blood mononuclear cells (PBMC) DNA using the Illumina 450K CpG array. Mediation analysis using linear regression models adjusted for age, ethnicity, and smoking was conducted to identify and assess the association between HDI exposure, CpG methylation, and urine HDA biomarker levels. We did not identify any CpGs common to HDI exposure and biomarker level suggesting that CpG methylation is a mediator that only partially explains the phenotype. Functional significance of genic- and intergenic-CpG methylation status was tested using protein-protein or protein-DNA interactions and gene-ontology enrichment to infer networks. Combined, the results suggest that methylation has the potential to affect HDI mass transport, permeation, and HDI metabolism. We demonstrate the potential use of PBMC methylation along with quantitative exposure and biomarker data to guide further investigation into the mediators of occupational exposure and biomarkers and its role in risk assessment. [Description provided by NIOSH]
• Subjects:
  Biomarkers Blood Chemistry Occupational Health Paint Risk Assessment Risk Factors Safety Skin Urine
• Keywords:
  1,6-Hexamethylene Diamine 1,6-Hexamethylene Diisocyanate Author Keywords: DNA Methylation Blood-cells Chemical-composition Chemical-properties Exposure-levels Exposure Assessment Genome-wide Analysis Models Paint-spraying Paints Proteins Risk-factors Urinalysis Urine Biomarker

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• ISSN:
  0378-4274
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  New York ; North Carolina ; OSHA Region 10 ; OSHA Region 2 ; OSHA Region 4 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  217-226
• Volume:
  231
• Issue:
  2
• NIOSHTIC Number:
  nn:20045828
• Citation:
  Toxicol Lett 2014 Dec; 231(2):217-226
• Contact Point Address:
  Leena A. Nylander-French, CIH Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, CB #7431, Chapel Hill, NC 27599-7431
• Email:
  leena_french@unc.edu
• CAS Registry Number:
  Hexamethylene diisocyanate (CAS RN 822-06-0) ; Hexamethylenediamine (CAS RN 124-09-4)
• Federal Fiscal Year:
  2015
• Performing Organization:
  University of North Carolina, Chapel Hill, North Carolina
• Peer Reviewed:
  True
• Start Date:
  20030801
• Source Full Name:
  Toxicology Letters
• End Date:
  20070731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:c76e9ee2b5fa15181a6132897f6788ace8bab2608323e2b2d9c78878946235b489e7c49bb5349a36df30979007f6fcdfe6207a1bca56728d91c557cfb4e98428
• Download URL:
  https://stacks.cdc.gov/view/cdc/201102/cdc_201102_DS1.pdf
• File Type:
  [PDF - 1.46 MB ]