Predicting in vivo gene expression in macrophages after exposure to benzo(a)pyrene based on in vitro assays and toxicokinetic/toxicodynamic models

Autor: Sophie Desmots, Olivier Fardel, Magali Boize, Céline Brochot, Lydie Sparfel, Alexandre R.R. Pery
Přispěvatelé: Institut National de l'Environnement Industriel et des Risques (INERIS), Service des études médicales, EDF-GDF, Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes (UR), French Ministry in charge of Ecology and Sustainable Development, within the framework of Programmes 189 and 190 - the European Commission 6th Framework Program, Priority 6 (Global change and ecosystems), project 2-FUN [contract #036976], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Rok vydání: 2010
Předmět:
Male
Physiologically based pharmacokinetic modelling
PBPK
Toxicodynamics
MESH: Gene Expression
MESH: Rats
Model calibration
Gene Expression
MESH: Rats
Sprague-Dawley
Biology
Pharmacology
Toxicology
BaP
Models
Biological
MESH: Dose-Response Relationship
Drug
Rats
Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
MESH: Benzo(a)pyrene
In vivo
Benzo(a)pyrene
Toxicokinetics
Animals
MESH: Animals
Pharmacokinetics
030304 developmental biology
0303 health sciences
Dose-Response Relationship
Drug
Macrophages
In vitro toxicology
MESH: Models
Biological
MESH: Macrophages
General Medicine
MESH: Pharmacokinetics
In vitro
MESH: Male
3. Good health
Rats
chemistry
030220 oncology & carcinogenesis
[SDV.TOX]Life Sciences [q-bio]/Toxicology
Pyrene
Vitro-vivo extrapolation
Zdroj: Toxicology Letters
Toxicology Letters, 2011, 201 (1), pp.8-14. ⟨10.1016/j.toxlet.2010.11.017⟩
Toxicology Letters, Elsevier, 2011, 201 (1), pp.8-14. ⟨10.1016/j.toxlet.2010.11.017⟩
ISSN: 1879-3169
0378-4274
DOI: 10.1016/j.toxlet.2010.11.017⟩
Popis: International audience; Predictive toxicology aims at developing methodologies to relate the results obtained from in vitro experiments to in vivo exposure. In the case of polycyclic aromatic hydrocarbons (PAHs), a substantial amount of knowledge on effects and modes of action has been recently obtained from in vitro studies of gene expression. In the current study, we built a physiologically based toxicokinetic (PBTK) model to relate in vivo and in vitro gene expression in case of exposure to benzo(a)pyrene (BaP), a referent PAH. This model was calibrated with two toxicokinetic datasets obtained on rats exposed either through intratracheal instillation or through intravenous administration and on an in vitro degradation study. A good agreement was obtained between the model's predictions and the concentrations measured in target organs, such as liver and lungs. Our model was able to relate correctly the gene expression for two genes targeted by PAHs, measured in vitro on primary human macrophages and in vivo in rat macrophages after exposure to BaP. Combining in vitro studies and PBTK modeling is promising for PAH risk assessment, especially for mixtures which are more efficiently studied in vitro than in vivo.
Databáze: OpenAIRE
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