Skip to Main content Skip to Navigation
Theses

Recherche de nouveaux biomarqueurs d'exposition aux hydrocarbures aromatiques polycycliques à travers l'étude des lésions de l'ADN chez l'homme

Caroline Marie 1
1 EPSP
TIMC - Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525
Abstract : PAH are ubiquitous environmental pollutants. Some of them, including benzo[a]pyrene (B[a]P) are carcinogenic to humans. It is therefore important to evaluate individual B[a]P exposure. For that purpose, the measurement of DNA adducts is of major interest since it allows the evaluation the genotoxic dose. Two metabolic pathways of B[a]P lead to the formation of several DNA adducts. In order to define new biomarkers of B[a]P exposure, we have aimed to determine the chemical nature of major adducts generated in human cells including keratinocytes and hepatocytes exposed to B[a]P. For such a purpose, an analytical method involving high performance liquid chromatography coupled to tandem mass spectrometry was set up allowing a specific detection of seven DNA adducts, with a limit of detection in the order of 1 adduct/108 normal nucleosides. Using such an approach, we have shown that the stable adducts of B[a]P diol-epoxyde (BPDE) are the major adducts generated in cellular DNA upon B[a]P exposure. Important differences in terms of kinetics of adducts formation and elimination were found between the two cell types. Attempts to measure the BPDE adducts in the urine of PAH occupationally exposed workers or in the DNA of lymphocytes of smokers were unsuccessful. Moreover, oxidative nucleosides when measured in human urine are not good biomarkers of effect to PAH. Stable BPDE adducts appear as pertinent biomarkers of exposure to B[a]P but the limit of detection of our assay needs to be improved to allow the measurement of adducts in humans.
Document type :
Theses
Complete list of metadatas

https://tel.archives-ouvertes.fr/tel-00196858
Contributor : Caroline Marie <>
Submitted on : Thursday, December 13, 2007 - 4:34:19 PM
Last modification on : Thursday, November 19, 2020 - 3:56:09 PM
Long-term archiving on: : Monday, April 12, 2010 - 7:25:06 AM

Identifiers

  • HAL Id : tel-00196858, version 1

Collections

Citation

Caroline Marie. Recherche de nouveaux biomarqueurs d'exposition aux hydrocarbures aromatiques polycycliques à travers l'étude des lésions de l'ADN chez l'homme. Autre [q-bio.OT]. Université Joseph-Fourier - Grenoble I, 2007. Français. ⟨tel-00196858⟩

Share

Metrics

Record views

1043

Files downloads

1748