Ignite Creation Date:
2024-05-06 @ 6:27 PM
Last Modification Date:
2024-10-26 @ 2:49 PM
Study NCT ID:
NCT05679544
Status:
RECRUITING
Last Update Posted:
2024-06-03
First Post:
2022-12-23
Brief Title:
Biological Signatures Resulting From Occupational Exposure to Complex Mixtures of PAHs
Sponsor:
University Hospital Grenoble
Organization:
University Hospital Grenoble
Study Overview
Official Title:
Biological Signatures Proteomics Metabolomics and Genotoxicity Associated With Occupational Exposure to PAH Mixtures and Relation With Exposure Biomarkers Support for the Derivation of Biological Limit Values
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PAH-ProMetGen
Brief Summary:
This research project aims at better understanding the early biological effects resulting from occupational exposure to complex Polycyclic Aromatic Hydrocarbon PAH mixtures
Current biomarkers used as part of biomonitoring campaigns are biomarkers of exposure not numerous and poorly related to health effects
The aim of this study is thus to improve our understanding of biological consequences of such exposures both in terms of proteins deregulation metabolism deregulation and genotoxicity
Current biomarkers used as part of biomonitoring campaigns are biomarkers of exposure not numerous and poorly related to health effects
The aim of this study is thus to improve our understanding of biological consequences of such exposures both in terms of proteins deregulation metabolism deregulation and genotoxicity
Detailed Description:
PAHs are ubiquitous pollutants inducing several diseases among which cancer is the most significant endpoint with increased incidences of lung skin and bladder cancers PAHs induce genotoxic effects sister chromatids exchange micronuclei DNA damage but require metabolic activation in humans as indirect-acting carcinogens Thus the knowledge of metabolic pathways involved following PAH exposure is critical for understanding and preventing cancer risks Besides exposure to PAHs is assumed to induce other adverse health effects diabetes inflammation infertility cardiovascular disease Unfortunately early disease-related biomarkers are still largely unknown and our comprehension about the mechanisms involved is still limited The rare existing biological limit values either refer to not carcinogenic PAH pyrene or detoxification pathways 3-OHBaP for BaP although new biomarkers reflecting the genotoxic pathway of BaP TetraolBaP are now available There is thus a need for identifying more relevant biomarkers of exposure effect and for a better understanding of the biological consequences resulting from PAH exposures as well as the associated metabolic pathways involved
The objectives of the project are
To better understand and characterize molecular metabolic and genotoxic impacts resulting from exposure to PAHs and to link such impacts with biological levels of various PAH metabolites
To study the influence of BaP metabolism genotoxic versus detoxication pathway on the differential expression of metabolites proteins and on genotoxicity endpoints in order to get relevant data for deriving new biological limit values
To elucidate the associations between omics deregulations due to PAH exposures and activated metabolic pathways in order to define candidate effect biomarkers for human biomonitoring
The originalities of the project are the following First this is a human study performed in real occupational settings on workers exposed to representative PAH mixtures It is a multidisciplinary approach simultaneously combining up-to-date biomonitoring omics and cytogenetics analyses that will give insight into a comprehensive view of metabolic reactions and protein expressions following occupational exposure to PAH mixtures and allow the identification of the biological processes involved Carcinogenic BaP metabolites Tetraol-BaP and 3-OHBaP will be simultaneously analyzed in order to compare the two main metabolic pathways of BaP
The main steps of the projects will be
Recruitment of 100 workers differentially exposed to PAH mixtures sampled across two time periods after weeks of exposure and following 3 weeks without occupational exposure
Recording of relevant data work characteristics jobs tasks working experience number of years of exposure smoking habits nutritional intake co-morbidity
Toxicological analyses LC-Fluorescence and GC-MS-MS of urinary metabolites of several gaseous and particulate PAHs Naphtalene Fluorene Phenanthrene Pyrene BaP BeP Chrysene BenzobFluoranthene BenzokFluoranthene BenzoaAnthracene
Proteomics analyses on blood samples through an enrichment approach for a bottom-up label free quantitative proteomic analysis based LC-HR-MS Deregulated proteins DEP will be identified and the associated protein signature A gene ontology GO analysis will define the groups of biological processes involved
Untargeted Metabolomics analyses on blood samples in UHPLC-HR-MS with unsupervised statistical analyses Principal Component Analysis Logistic Regressions identification of relevant metabolites by their comparison to the Human Metabolome database and advanced molecular networking spectral library search of LC-MSMS data
Micronuclei MN in buccal cells through the harvesting of buccal cells using a cytobrush transfer to the lab in a buffer fixing and staining automatic counting under fluorescent light
The objectives of the project are
To better understand and characterize molecular metabolic and genotoxic impacts resulting from exposure to PAHs and to link such impacts with biological levels of various PAH metabolites
To study the influence of BaP metabolism genotoxic versus detoxication pathway on the differential expression of metabolites proteins and on genotoxicity endpoints in order to get relevant data for deriving new biological limit values
To elucidate the associations between omics deregulations due to PAH exposures and activated metabolic pathways in order to define candidate effect biomarkers for human biomonitoring
The originalities of the project are the following First this is a human study performed in real occupational settings on workers exposed to representative PAH mixtures It is a multidisciplinary approach simultaneously combining up-to-date biomonitoring omics and cytogenetics analyses that will give insight into a comprehensive view of metabolic reactions and protein expressions following occupational exposure to PAH mixtures and allow the identification of the biological processes involved Carcinogenic BaP metabolites Tetraol-BaP and 3-OHBaP will be simultaneously analyzed in order to compare the two main metabolic pathways of BaP
The main steps of the projects will be
Recruitment of 100 workers differentially exposed to PAH mixtures sampled across two time periods after weeks of exposure and following 3 weeks without occupational exposure
Recording of relevant data work characteristics jobs tasks working experience number of years of exposure smoking habits nutritional intake co-morbidity
Toxicological analyses LC-Fluorescence and GC-MS-MS of urinary metabolites of several gaseous and particulate PAHs Naphtalene Fluorene Phenanthrene Pyrene BaP BeP Chrysene BenzobFluoranthene BenzokFluoranthene BenzoaAnthracene
Proteomics analyses on blood samples through an enrichment approach for a bottom-up label free quantitative proteomic analysis based LC-HR-MS Deregulated proteins DEP will be identified and the associated protein signature A gene ontology GO analysis will define the groups of biological processes involved
Untargeted Metabolomics analyses on blood samples in UHPLC-HR-MS with unsupervised statistical analyses Principal Component Analysis Logistic Regressions identification of relevant metabolites by their comparison to the Human Metabolome database and advanced molecular networking spectral library search of LC-MSMS data
Micronuclei MN in buccal cells through the harvesting of buccal cells using a cytobrush transfer to the lab in a buffer fixing and staining automatic counting under fluorescent light
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2022-A01590-43 | OTHER | IDRCB | None |