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

Details

• Alternative Title:
  Toxicol Lett
• Personal Author:
  Nylander-French, Leena A. ; Wu, Michael C. ; French, John E. ; Boyer, Jayne C. ; Smeester, Lisa ; Sanders, Alison P. ; Fry, Rebecca C.
• 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.
• Subjects:
  1,6-Hexamethylene Diamine 1,6-Hexamethylene Diisocyanate Adult Article Biomarkers DNA Methylation Exposure Assessment Gene Expression Regulation Genome-wide Analysis Humans Isocyanates Male Middle Aged Occupational Exposure Urine Biomarker Young Adult

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• Source:
  Toxicol Lett. 231(2):217-226
• Pubmed ID:
  25445006
• Pubmed Central ID:
  PMC8060918
• Document Type:
  Journal Article
• Funding:
  T42 OH008673/OH/NIOSH CDC HHS/United States ; R01 OH007598/OH/NIOSH CDC HHS/United States ; R21 OH010203/OH/NIOSH CDC HHS/United States ; R21-OH010203/OH/NIOSH CDC HHS/United States ; T42OH008673/ACL/ACL HHS/United States ; R01-OH007598/OH/NIOSH CDC HHS/United States ; P42 ES005948/ES/NIEHS NIH HHS/United States ; T42/CCT422952/PHS HHS/United States ; P30 ES010126/ES/NIEHS NIH HHS/United States ; T42/OH-008673/OH/NIOSH CDC HHS/United States
• Volume:
  231
• Issue:
  2
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:73b1b2e314af75b3aab71de2e72fbbe155c8a26fe748a9effda3d82dbae36f57
• Download URL:
  https://stacks.cdc.gov/view/cdc/105467/cdc_105467_DS1.pdf
• File Type:
  [PDF - 1.17 MB ]