Identification of new tetrahydroxylated metabolites of Polycyclic Aromatic Hydrocarbons in hair as biomarkers of exposure and signature of DNA adduct levels

Nathalie Grova*, Jean Philippe Antignac, Emilie M. Hardy, Fabrice Monteau, Karine Pouponneau, Bruno Le Bizec, Brice M.R. Appenzeller

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

Abstract

The present study addresses the hypothesis that the concentration of tetrahydroxylated Polycylic Aromatic Hydrocarbons (tetra-OH-PAHs) in hair might be a useful biomarker of human exposure to PAHs, providing quantitative assessment of the internal dose, as well as information on the associated toxicity in relation to individual's specific metabolism. By means of animal models, this work aimed at identifying new tetra-OH-PAHs which can be released from the hydrolysis of DNA-adducts and can also be directly detected in biological matrices usually used in the field of biomonitoring such as hair and urine. Results obtained from a targeted gas chromatography coupled with tandem mass spectrometry (GC-MS/MS) approach, demonstrated the presence of 8 tetrahydroxylated metabolites in DNA and 23 in hairs of rats exposed to mixtures of PAHs, which had never been analyzed before. Ten tetra-OH-PAHs were clearly characterized by using their analytical standards, corresponding to 4 parent PAHs (phenanthrene, chrysene, benz[a]anthracene and benzo[a]pyrene) whereas 13 tetra-OH-PAHs from 3 other parents (anthracene, fluoranthene and benz[k]fluoranthene) were detected but not yet characterized. No tetrahydroxylated metabolite has been clearly identified for naphthalene, fluorene, benzo[b]fluoranthene, benzo[g,h,i]perylene, or dibenzo[a,h]anthracene, which can all potentially form adducts. The relevance of tetra-OH-PAH analysis in hair as biomarkers of PAH exposure was evaluated in a dose-response study conducted on 64 rats (Long Evans females/n = 8 per groups) under repeated exposure (3 times per week) to a mixture of 16 PAHs at low doses (0.01–0.8 mg/kg) for 90 days. Most of the tetra-OH-PAHs targeted in the method were detected in the hairs of the rats, regardless of the dose of exposure. Significant linear relationships (R2 ranging from 0.558 to 0.964, p < 0.001) were observed between the administered dose and the tetra-OH-PAH concentrations in the hairs for 20 out of the 23 metabolites. By widening the range of PAH metabolites used as biomarkers of exposure so as to include the analysis of PAH tetrahydroxylated forms (especially those exhibiting more than 5 aromatic rings), the present methodology will enable multi-exposure assessments which are more accurately representative of actual situations of exposure to PAHs.

Original languageEnglish
Pages (from-to)65-76
Number of pages12
JournalAnalytica Chimica Acta
Volume995
DOIs
Publication statusPublished - 1 Dec 2017

Keywords

  • DNA
  • GC-API-HRMS
  • GC-MS/MS
  • Hair
  • Polycyclic Aromatic Hydrocarbons
  • Tetrahydroxylated metabolites

Fingerprint

Dive into the research topics of 'Identification of new tetrahydroxylated metabolites of Polycyclic Aromatic Hydrocarbons in hair as biomarkers of exposure and signature of DNA adduct levels'. Together they form a unique fingerprint.

Cite this