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Formaldehyde-Induced DNA Adducts as Biomarkers of In Vitro Human Nasal Epithelial Cell Exposure to Formaldehyde



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  • Personal Author:
  • Description:
    Formaldehyde (FA) is a mutagen that, at high concentrations and long durations, has been reported to cause nasal cancer in rats and in some humans. The level of FA-induced modified DNA in nasal cells should serve as a biomarker of FA exposure and effect. In the present study, a high-performance liquid chromatography (HPLC)-ultraviolet (UV) method at 254 nm was developed and optimized to detect and quantify hydroxymethyldeoxynucleosides after the isolated DNA in exposed human nasal epithelial cells (HNEC) was enzymically digested. Normal and modified deoxynucleosides were successfully resolved from one another and from tissue and enzyme blank interferences. The viability of HNEC exposed to FA in solution for 24 h decreased, and there was a linear dose response between % nonviability and FA dose from 10 to 500 ug/mL. Amounts of 18.0 +/- 1.5 pmol N6-dA and 12.0 +/- 1.2 pmol N2-dG derivatives were determined in a 10 µL injection after 1.4 × 107 HNEC (106 µg DNA) were exposed to 500 µg/mL in solution. The respective tissue concentrations in pmol hydroxymethyldeoxynucleoside/mg DNA were 170 +/- 14 and 113 +/- 11. The lower quantifiable limits were about 97 and 88 pmol/mg DNA, respectively. Diffusive exposure of HNEC to air FA up to 100 ppm (v/v) for 24 h did not produce quantifiable hydroxymethylnucleosides. FA-modified deoxynucleosides may be useful biomarkers for FA exposure in biological monitoring samples taken by nasal lavage or brush biopsy. [Description provided by NIOSH]
  • Subjects:
  • Keywords:
  • ISSN:
    1383-5718
  • Document Type:
    Text
  • Funding:
    Grant
  • Genre:
    Journal Article
  • Place as Subject:
  • CIO:
    National Institute for Occupational Safety and Health (NIOSH)
  • Topic:
    Workplace Safety & Health
  • Location:
    North America
  • Pages in Document:
    13-24
  • Volume:
    563
  • Issue:
    1
  • NIOSHTIC Number:
    nn:20057950
  • Citation:
    Mutat Res Genet Toxicol Environ Mutagen 2004 Sep; 563(1):13-24
  • Contact Point Address:
    Shane S. Que Hee, Department of Environmental Health Sciences and UCLA Center for Occupational and Environmental Health, School of Public Health, University of California at Los Angeles, 650 Charles Young Jr Drive South, Los Angeles, CA 90095-1772, USA
  • Email:
    squehee@ucla.edu
  • CAS Registry Number:
    Formaldehyde (CAS RN 50-00-0)
  • Federal Fiscal Year:
    2004
  • Performing Organization:
    University of California, School of Public Health, Los Angeles, CA
  • Peer Reviewed:
    True
  • Start Date:
    19990701
  • Source Full Name:
    Mutation Research - Genetic Toxicology and Environmental Mutagenesis
  • End Date:
    20040630
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:a2003e6f46f9b27cd33d445a9cfa2b804f351dd9d3e6367f6cfc31e91d50c820b93448d380f0b7be5be18be2380166d7aaab0080acd223161be5b4096f53e9fb
  • Download URL:
  • File Type:
    Filetype[PDF - 207.59 KB ]
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