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Table of contents
1. Introduction
1.1. Background
1.2. Health hazards in the workplace of sewage workers
1.2.1. Biological and physical hazards
1.2.2. Chemical hazard
1.3. Characterization of exposure among sewage workers
1.3.1. Sewage drains indoor air pollution
1.3.1.1. Polycyclic aromatic hydrocarbons (PAHs)
1.3.1.2. Volatile organic compounds (VOCs)
1.3.2. Other exposures in sewage system (skin contact and ingestion)
1.4. Health effects among sewage workers
1.4.1. Morbidity studies
1.4.2. Mortality and cancer studies
1.5. Biomarkers of exposure to genotoxicants
1.5.1. In vitro comet assay
1.5.1.1. History and definition
1.5.1.2. General principle of the assay
1.5.1.3. Fields of application
1.5.2. In vitro micronucleus assay
1.5.2.1. History and definition
1.5.2.2. General principle of the assay
1.5.2.3. Fields of application
1.5.3. Comet and micronucleus assays in vitro human occupational studies
1.6. Biomarkers of early effects of genotoxicants
1.6.1. The 24h urinary 8-oxodG
1.6.2. DNA-adducts
1.6.3. Metabolism of caffeine and CYP1A2 activity
1.7. Description of the parisian sewage system
1.8. Rationale and justification of the study
1.9. Aim of the study
1.10. Study hypothesis
1.11. Thesis overview
2. Materials and methods
2.1. Protocol development
2.1.1. Study protocol article (1st article)
2.1.2. Comet article (2nd article)
2.1.3. Validation of urine extraction protocol on comet assay
2.1.4. Validation of micronucleus assay on B[a]P using Hep G2 cells
2.1.5. Urinary caffeine metabolites and assessment of CYP1A2 activity
2.2. Epidemiological study
2.2.1. Details out of protocol article
2.2.1.1. Study setting, administrative and ethical consideration
2.2.1.2. Sample size
2.2.1.3. Recruitment procedure and data collection
2.2.2. Details on the tests out of the article
2.2.2.1. Blood samples
2.2.2.2. Treatment of urine samples
2.2.2.3. Extraction of organic fraction from urine samples
2.2.2.4. Cellular line used (Hep G2)
2.2.2.5. Chemicals and media for cell culture
2.2.3. Comet assay
2.2.3.1. The solutions used
2.2.3.2. Culture and treatment of cellular line used (Hep G2)
2.2.3.3. Methodology
2.2.3.4. Selection of comets and image analysis parameter used
2.2.4. Micronucleus assay
2.2.4.1. The solutions used
2.2.4.2. Methodology
2.2.4.3. Selection and calculation of the parameters
2.2.5. Sewage system‟s indoor air sampling protocol
2.2.5.1. Sampling and collection of pahs and VOCs
2.2.5.2. Extraction and analysis of PAHs
2.2.5.3. Extraction and analysis of VOCs
2.2.6. Measurement of 24h urinary 8-oxodG
2.2.7. Statistical analysis
3. Results
3.1. Exposure and genotoxicity article (3rd article)
3.2. Multivariate analysis of in vitro assays with the study groups
3.3. Population characteristics factors and 8-oxodG associations
3.4. Multivariate analysis of 8-oxodG with the study groups
3.5. Multivariate analysis of 8-oxodG with exposure duration
3.6. The associations between 8-oxodG and workplace air pollutants
3.7. The association between the two biomarkers of exposure
4. General discussion
4.1. The study‟s main results
4.2. The results of urinary caffeine metabolites and CYP1A2 activity
4.3. Cancer risk estimates and workplace sampling
4.4. The urinary biomarkers of exposure associations
4.5. The early effect biomarker (8-oxodG) associations
4.6. Choice of the cellular line (Hep G2)
4.7. The study sample size
4.8. Study questionnaires
4.9. Bias of the study
5. Conclusion and research perspectives
Sommaire (Français)
General references
Partnerships of the study
Funding of the study
Appendices
Résumé
Abstract
