Kristian Dreij

About me

Kristian Dreij received his Ph.D. degree in Toxicology in 2005 from the lab of Prof. Jernström at Karolinska Institutet (KI). In 2006 he joined as a post doc in the lab of Prof. Scicchitano at New York University. In 2009 he was recruited to the group of Prof. Stenius, KI as a post-doctoral fellow focusing on genetic toxicology. Since 2012 he has led a research group at the Institute of Environmental Medicine, KI with focus on genotoxic and mutagenic effects of complex environmental mixtures such as air pollution. Kristian became Associate Professor/Docent in Toxicology at KI in 2016. He is also Deputy Program Director of the global Master's Programme in Toxicology at Karolinska Institutet.

Research description

Mutational signatures of environmental complex mixtures.

Experimentally determined mutational signatures have provided important insights into the agents and processes underlying the causes of human cancer. Although humans mainly are exposed to complex mixtures of agents which might contribute to cancer development, this research has so far exclusively focused on single mutagens. The overall objective of this project is to determine mutational signatures induced by environmental complex mixtures in human cells, thereby increasing the understanding of the mechanisms and role of mixtures vs single compounds in cancer etiology. This project is funded by the Swedish Research Council and Karolinska Institutet.

 

Interactions between PAHs and other environmental pollutants and toxicological effects.

One major group of environmental pollutants is the polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene, which have been linked with numerous adverse health effects including cancer, cardiovascular and developmental effects. The goal of this project is to investigate the harmful effects of exposure to mixtures of PAHs and other environmental pollutants, and to improve the scientific base for risk assessment of human exposure to complex environmental mixtures. In the project we study the mixture effects on DNA damage and repair, inflammation and development using human cell lines (Jarvis et al 2013, Jarvis et al 2014) and zebrafish (Danio rerio) embryos (Wincent et al 2015, Cunha et al 2020, Ünlü Endirlik et al 2023). Our conclusion is that synergistic mixture effects between different PAHs and other pollutants represent a major effect and there is an urgent need to include these interactions in health risk assessment (Jarvis et al 2014). We are currently studying how toxicokinetics impact on toxicodynamics of more polar PAHs in collaboration with Dr Vogs at SLU, Uppsala. This project is funded by the Swedish Research Council and Karolinska Institutet.

 

Development of new approach methodologies for assessing cancer risks associated with air pollution mixtures.

Air pollution is a complex mixture of compounds with different biological activities that makes risk assessment a challenge. Air pollution in general, as well as many of its components, is classified as carcinogens. Current strategies for cancer risk assessment (CRA) of air pollution are however based on a pollutant-by-pollutant approach. This is a great simplification and excludes the possibility of mixture effects that may underestimate actual human health risks. The objective of this project is to address these issues by developing new approach methodologies (NAMs) for CRA of air pollution mixtures. We suggest that CRA of complex mixtures should be based on toxicity testing of whole mixtures in vitro and determination of relative Mixture Potency Factors (MPFs) (Jarvis et al 2013, Jarvis et al 2014). We have also showed that this approach can accurately determine genotoxic potency of single air pollutants (Lim et al 2015, Dreij et al 2017). Applying this NAM, we show that CRA of air pollution based on in vitro MPFs better predict the lung cancer risk associated with exposure to ambient air PM than currently accepted component-based approaches (Dreij et al 2017). In addition, MPFs for different Standard Reference Materials (SRMs) have been validated against Salmonella mutgenicity and in vivo carcinogenicity data (de Oliveira Galvao et al 2022). We are now applying this NAM with samples representing different emission sources and environments. This project is funded by the Swedish Research Council, STINT/CAPES, Swedish Cancer and Allergy fund and Karolinska Institutet.

 

Biological consequences of transcriptional errors induced by DNA damage.

When a DNA-damage is bypassed during transcription this can lead to RNA misincorporation, a process termed transcriptional mutagenesis (TM). Although the concept of TM is well known, the biological consequences are still a recent discovery. While the few existing studies of TM have begun to shed light on the process, many issues have yet to be addressed. The extent, to which TM occurs in mammalian cells and the role these seemingly transient errors might play in disease processes such as carcinogenesis, is currently unknown. We show that TM at a splice site significantly reduces splicing fidelity, thereby changing the relative expression of alternative disease-related splicing forms in mammalian cells (Paredes et al 2017). Current theories postulate that the transient expression of mutant proteins via TM could play a major role in tumor development by allowing it to escape growth-inhibitory apoptotic signals and undergo clonal expansion. We show that O6-meG-induced TM reduces the p53 tumor-suppressor function through deregulation of cell cycle control and impaired activation of apoptosis in human cells (Ezerskyte et al 2018, Liang et al 2020). This project is funded by the Swedish Research Council and Karolinska Institutet. More information.

 

Genotoxic evaluation in Bolivian populations exposed to mixtures of pesticides.

In this project we are conducting a cross-sectional study among the Bolivian agricultural population. In Bolivia, farmers have increased the use of pesticides to enter into a more competitive international market. There is little or no social protection which together leads to hazardous working conditions for the farmers. To evaluate and study the correlation between exposure to pesticides and risk of developing genotoxic effects we use questionnaire information and blood and urine analysis. Our results show a strong correlation between use of personal protection equipment, exposure levels and risk of genotoxic damage among the farmers (Barron Cuenca et al 2019, Barron Cuenca et al 2020). It was also found that high exposure to certain mixtures of pesticides (containing mainly 2,4-D or cyfluthrin) was significantly associated with increased level and risk of genotoxic damage, suggesting that their use should be better controlled or limited. Testing some of these mixtures in vitro confirmed the genotoxic effects and highligthed oxidative stress as a possible important mechanism (Barron Cuenca et al 2022). This project is funded by the Swedish Research Council and SIDA. More information.

 

 

Research group

• Felipe De Oliveira Galvao, research specialist
• Gildacio Chaves, post doc
• Caroline Scaramboni, PhD student (primary affiliation University of São Paulo)
• Carla Martins, PhD student (primary affiliation Universidade Nova de Lisboa)
• Susana Moreira, visiting professor from UFRN