Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Researcher Maurizio Gualtieri, University of Milano-Bicocca, Italy
- Second opponent: Senior Researcher Julia Catalán Rodríguez, Finnish Institute of Occupational Health
- Third member and chair of the evaluation committee: Professor II Arne Klungland, University of Oslo
Chair of the Defence
Professor Torkel Hafting, University of Oslo
Principal Supervisor
Senior Scientist Elise Rundén-Pran, NILU
Summary
Humans are constantly exposed to particles from the surrounding environment, including nanomaterials (NMs) which are small particles with size <100 nm. After inhalation, some NMs can deposit in the lungs, cross the lung-blood barrier, and reach other target organs such as the liver. New approach methodologies are being developed for hazard assessment of NMs, including advanced in vitro models based on cell cultures in more physiologically relevant conditions. Of special importance is the application of these models for genotoxicity testing, to evaluate the ability of the NMs to alter the genetic information.
The aim of this work was to contribute to the development of advanced lung and liver models, representing a first-contact and secondary target organ of inhaled NMs, respectively. The performance of the models in genotoxicity testing was compared to traditional models.
Advanced lung models were constructed with bronchial or alveolar epithelial cells in mono- or cocultures with endothelial cells and macrophages at the air-liquid interface. An advanced liver model was constructed with hepatocytes cultured in spheroids, allowing increased cell-to-cell interactions and signaling. Both advanced models and traditional models were exposed to NMs or chemicals for 24 hours, before cellular viability, genotoxicity, inter-laboratory variability, and other endpoints were analyzed.
This work has shown that the culturing conditions of the cells affected the toxic response to chemicals and NMs. This thesis contributed to new knowledge on advanced in vitro models by application of genotoxicity testing after NM exposures. Comet assay was applied to HepG2 spheroids and micronucleus assay to ALI cocultures for the first time to our knowledge. The advanced models are promising 3D models for use in genotoxicity studies and can support the hazard and risk assessment of NMs in compliance with the 3R´s for next generation risk assessment.
Additional information
Contact the research support staff.