Kristian Dreij

Kristian Dreij
Karolinska Institutet | KI · Institute of Environmental Medicine - IMM

PhD

About

77
Publications
11,216
Reads
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1,253
Citations
Introduction
Kristian Dreij currently works at the Institute of Environmental Medicine - IMM, Karolinska Institutet. Kristian does research in Molecular Biology, Genetics and Cell Biology. Their most recent publication is 'O 6 -methylguanine–induced transcriptional mutagenesis reduces p53 tumor-suppressor function'.
Additional affiliations
January 2016 - present
Karolinska Institutet
Position
  • Professor (Associate)
January 2015 - present
Karolinska Institutet
Position
  • Director of studies
Description
  • Director of studies at the global Master program in toxicology at Karolinska Institutet.
September 2010 - December 2015
Karolinska Institutet
Position
  • Professor (Assistant)

Publications

Publications (77)
Article
Oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) are found in the environment together with PAHs. However, less is known concerning their biological activity including their impact on aryl hydrocarbon receptor (AHR) signalling and the subsequent modulation of the cytochrome P450 monooxygenases (CYP). In this study, effects of 15 environmental...
Article
In this review we discuss the effects of exposure to complex PAH mixtures in vitro and in vivo on mechanisms related to carcinogenesis. Of particular concern regarding exposure to complex PAH mixtures is how interactions between different constituents can affect the carcinogenic response and how these might be included in risk assessment. Overall t...
Article
Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are present in air particulate matter (PM) and have been associated with many adverse human health effects including cancer and respiratory disease. However, due to their complexity, the risk of exposure to mixtures is difficult to estimate. In the present study the effects of binary mixtu...
Article
Full-text available
O6-Methylguanine (O6-meG), which is produced in DNA following exposure to methylating agents, instructs human RNA polymerase II to mis-insert bases opposite the lesion during transcription. In this study, we examined the effect of O6-meG on transcription in human cells and investigated the subsequent effects on protein function following translatio...
Article
The polycyclic aromatic hydrocarbons (PAHs) dibenzo[a,l]pyrene (DBP) and benzo[a]pyrene (BP) are widespread environmental contaminants and potent carcinogens. The fjord-region DBP is considerably more carcinogenic than the bay-region BP. This fact can be ascribed to differences in DNA binding efficiency of their ultimate carcinogenic diol epoxide (...
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Whole mixture-based testing using in vitro new approach methodologies (NAMs) has been suggested to facilitate the hazard and risk assessment of complex environmental mixtures. Previous studies have shown that phosphorylation of DNA damage signaling proteins checkpoint kinase 1 (pChk1) and histone 2AX (γH2AX) are sensitive markers that can be used f...
Article
We previously showed that farmers in Bolivia are exposed to many pesticides, some at elevated levels, and that this was associated with increased risk of genetic damage. To improve the understanding of possible mixture effects, the cytotoxicity and genotoxicity of pesticides were studied in vitro using human liver HepG2 cells. The studied pesticide...
Article
Polycyclic aromatic hydrocarbons (PAHs) are a large class of organic compounds produced from incomplete combustion. Many PAHs are mutagenic and some are carcinogenic and pose a health risk to humans. Dietary intake of PAHs is a major route of exposure, where fats and edible oils are important contributors to overall dietary PAH exposure. Composed o...
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Background: Cancer risk assessment of complex exposures, such as exposure to mixtures of polycyclic aromatic hydrocarbons (PAHs), is challenging due to the diverse biological activities of these compounds. With the help of text mining (TM), we have developed TM tools-the latest iteration of the Cancer Risk Assessment using Biomedical literature to...
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Interleukin (IL) 6 contributes to atherosclerotic plaque development through IL6 membrane-bound (IL6R and gp130) and soluble (sIL6R and sgp130) receptors. We investigated IL6 receptor expression in carotid plaques and its correlation with circulating IL6 and soluble receptor levels. Plasma samples and carotid plaques were obtained from 78 patients...
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Polycyclic aromatic compounds (PACs), including polycyclic aromatic hydrocarbons (PAHs) and oxygenated PAHs (oxy-PAHs), are common environmental pollutants known to cause health effects in humans and wild-life. In particular, vertebrate cardiovascular development and function are sensitive to PACs. However, the interactive effects of PAHs and oxy-P...
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Children spend a significant amount of their day in preschool; thus, environmental quality at preschools may have an impact on children's health. In the present study, we analyzed polycyclic aromatic compounds (PACs), including PAHs, alkylated PAHs and oxygenated PAHs (OPAHs), in indoor and outdoor air particulate matter (PM10) and indoor dust at p...
Article
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Macroautophagy/autophagy is a conserved catabolic pathway that targets cytoplasmic components for their degradation and recycling in an autophagosome-dependent lysosomal manner. Under physiological conditions, this process maintains cellular homeostasis. However, autophagy can be stimulated upon different forms of cellular stress, ranging from nutr...
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The transcriptional error rate can be significantly increased by the presence of DNA lesions that instruct mis-insertion during transcription; a process referred to as transcriptional mutagenesis (TM) that can result in altered protein function. Herein, we determined the effect of O6-methylguanine (O6-meG) on transcription and subsequent transactiv...
Article
Full-text available
The use of pesticides has increased during the past decades, also increasing the risk of exposure to toxic pesticides that can cause detrimental health effects in the future. This is of special concern among farmers in low-to-middle-income countries that may lack proper training in the safe use of these chemicals. To assess the situation in Bolivia...
Article
Full-text available
An amendment to this paper has been published and can be accessed via a link at the top of the paper. In the original Article, co-author Ulla Stenius’ surname was misspelled as Ulla Steinus. This has been corrected in the PDF, HTML and XML versions of this Article.
Article
The extractable organic material (EOM) from atmospheric total suspended particles (TSP) contains several organic compounds including non‐substituted polycyclic aromatic hydrocarbons (PAHs), alkyl‐PAHs, and nitro‐PAHs. These chemicals seem to be among the key drivers of TSP genotoxicity. We have shown previously that the mutagenic potencies of the E...
Article
Polycyclic aromatic compounds (PACs) are ubiquitous pollutants that are found everywhere in our environment, including air, soil and water. The aim of this study was to determine concentrations, distribution, sources and potential health risk of 43 PACs in soils collected from 25 urban parks in Stockholm City, Sweden. These PACs included 21 PAHs, 1...
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Full-text available
The last decade witnessed extraordinary advances in “omics” methods, particularly transcriptomics, proteomics and metabolomics, enabling toxicologists to integrate toxicokinetics and toxicodynamics with mechanistic insights on the mode-of-action of noxious chemicals, single or combined. The toxicology of mixtures is, nonetheless, a most challenging...
Article
Approximately 3 billion people world-wide are exposed to air pollution from biomass burning. Herein, particulate matter (PM) emitted from artisanal cashew nut roasting, an important economic activity worldwide, was investigated. This study focused on: i) chemical characterization of polycyclic aromatic hydrocarbons (PAHs) and oxygenated (oxy-) PAHs...
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Full-text available
During the past decades, farmers in low to middle-income countries have increased their use of pesticides, and thereby the risk of being exposed to potentially genotoxic chemicals that can cause adverse health effects. Here, the aim was to investigate the correlation between exposure to pesticides and genotoxic damage in a Bolivian agricultural pop...
Article
Atmospheric particulate matter (PM) organic fraction from urban centers are frequently mutagenic for the Salmonella/microsome assay. This mutagenicity is related to both primary and secondary pollutants, and meteorological conditions have great influence in the secondary pollutant's formation. Our objective was to compare the mutagenicity of atmosp...
Article
Oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) are a group of environmental pollutants found in complex mixtures together with PAHs. In contrast to the extensively studied PAHs, which have been established to have mutagenic and carcinogenic properties, much less is known about the effects of oxy-PAHs. The present work aimed to investigate t...
Article
Transforming growth factor beta (TGFβ) is multi-functional cytokine that is involved in the co-ordination and regulation of many cellular homeostatic processes. Compromised TGFβ activity has been attributed to promotion of human cancers. Recent studies have identified a role for TGFβ in response to radiation-induced DNA damage, suggesting a link be...
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Altered protein function due to mutagenesis plays an important role in disease development. This is perhaps most evident in tumorigenesis and the associated loss or gain of function of tumor-suppressor genes and oncogenes. The extent to which lesion-induced transcriptional mutagenesis (TM) influences protein function and its contribution to the dev...
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We show for the first time that, in contrast to other glutathione transferases and peroxidases, deletion of microsomal glutathione transferase 1 (MGST1) in mice is embryonic lethal. To elucidate why, we used zebrafish development as a model system and found that knockdown of MGST1 produced impaired hematopoiesis. We show that MGST1 is expressed ear...
Article
Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants associated with adverse human health effects including cancer. However, the risk of exposure to mixtures is difficult to estimate and risk assessment by whole mixture potency evaluations has been suggested. To facilitate this, reliable in vitro based tes...
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Full-text available
Splicing fidelity is essential to the maintenance of cellular functions and viability, and mutations or natural variations in pre-mRNA sequences and consequent alteration of splicing have been implicated in the etiology and progression of numerous diseases. The extent to which transcriptional errors or lesion-induced transcriptional mutagenesis (TM...
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Micronucleus (MN) assay is extensively used to biomonitor aneuploidy and clastogenicity of genotoxic compounds. However, the suitability of this assay for early life stages of model fish species is still poorly documented. In this study, the determination of MN using flow cytometry was successfully applied for the first time to zebrafish (Danio rer...
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The widespread production and use of nanoparticles calls for faster and more reliable methods to assess their safety. The main aim of this study was to investigate the genotoxicity of three reference TiO2 nanomaterials (NM) within the frame of the FP7-NANoREG project, with a particular focus on testing the applicability of mini-gel comet assay and...
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Aim: Many transcription factors with importance in health and disease are redox regulated. However, how their activities may be intertwined in responses to redox perturbing stimuli is poorly understood. To enable in-depth characterization of this aspect, we here developed a methodology for simultaneous determination of Nrf2, HIF and NF-κB activati...
Article
Many industrial sites are polluted by complex mixtures of polycyclic aromatic compounds (PACs). Besides polycyclic aromatic hydrocarbons (PAHs) these mixtures often contain significant amounts of more polar PACs including oxygenated PAHs (oxy-PAHs). The effects of oxy-PAHs are however poorly known. Here we used zebrafish embryos to examine toxiciti...
Article
Benz[j]aceanthrylene (B[j]A) is a cyclopenta fused polycyclic aromatic hydrocarbon with strong mutagenic and carcinogenic effects. We have identified B[j]A in air particulate matter in samples collected in Stockholm, Sweden and in Limeira, Brazil using LC-GC/MS analysis. Determined concentrations ranged between 1.57-12.7 and 19.6-30.2 pg/m3 in Stoc...
Article
Transforming growth factor beta (TGFβ) is involved in coordinating a number of cellular processes including proliferation, differentiation and apoptosis, and as such, dysregulation of TGFβ signalling has significant implications for cancer development. TGFβ is rapidly and persistently activated in response to irradiation-induced DNA damage (Barcell...
Article
The Salmonella/microsome assay is the most used assay for the evaluation of air particulate matter (PM) mutagenicity and a positive correlation between strain TA98 responses and benzo[a]pyrene (B[a]P) levels in PM has been found. However, it seems that the major causes of PM mutagenicity in this assay are the nitro and oxy-PAHs. Salmonella YG5161,...
Article
Benzo[a]pyrene (B[a]P) is a known human carcinogen and is commonly used as a surrogate for assessing the carcinogenic risk posed by complex mixtures of polycyclic aromatic hydrocarbons (PAHs) present in air particulate matter (PM). However, studies have shown that using B[a]P as a surrogate may underestimate the carcinogenic potential of PAH mixtur...
Article
Polycyclic aromatic hydrocarbons (PAHs) are common environmental pollutants that occur naturally in complex mixtures. Many of the adverse health effects of PAHs including cancer are linked to the activation of intracellular stress response signaling. This study has investigated intracellular MAPK signaling in response to PAHs in extracts from urban...
Article
A human cell consists schematically of an outer cellular membrane, a cytoplasm containing a large number of organelles (mitochondria, endoplasmatic reticulum etc.), a nuclear membrane and finally the cellular nucleus containing DNA. The organelles create a complex and dense system of membranes or sub-domains throughout the cytoplasm. The mathematic...
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Embryonic development depends on complex and precisely orchestrated signaling pathways including specific reduction/oxidation cascades. Oxidoreductases of the thioredoxin family are key players conveying redox signals through reversible posttranslational modifications of protein thiols. The importance of this protein family during embryogenesis has...
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Exocrine pancreatic cancer is an aggressive disease with an exceptionally high mortality rate. Genetic analysis suggests a causative role for environmental factors, but consistent epidemiological support is scarce and no biomarkers for monitoring the effects of chemical pancreatic carcinogens are available. With the objective to identify common tra...
Data
Results obtained in Panc-1 cells arranged according to number of positive evidence related to ATX activation, MMP-9 activation and invasive growth. (DOCX)
Article
Polycyclic aromatic hydrocarbons (PAHs) are formed during incomplete combustion of organic material and are ubiquitous environmental contaminants. High levels of PAHs are commonly found in soils at industrial sites, thereby constituting a risk for humans and the environment. However, this risk is often difficult to estimate due to the complexity of...
Article
Full-text available
Mathematical modeling of reaction-diffusion system in a biological cell is an important and difficult task, especially when the chemical compounds are lipophilic. The difficulty level increases, when we take into account the heterogeneity of the cell, and the variation of cellular architecture. Mathematical modeling of reaction-diffusion systems in...
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A general description of effects of toxic compounds in mammalian cells is facing several problems. Firstly, most toxic compounds are hydrophobic and partition phenomena strongly influence their behaviour. Secondly, cells display considerable heterogeneity regarding the presence, activity and distribution of enzymes participating in the metabolism o...
Article
Polycyclic aromatic hydrocarbons (PAH) are an important class of environmental contaminants many of which require metabolic activation to DNA-reactive bay or fjord region diolepoxides (DE) in order to exert their mutagenic and carcinogenic effects. In this study, the mutagenicity of the bay region diolepoxides (+)-anti-7,8-dihydroxy-9,10-epoxy-7,8,...
Article
National Toxicology Program (NTP) performs two-year cancer bioassays. We have analyzed the NTP rat data base and searched for gender differences in susceptibility to carcinogens. We identified 10 chemicals that induced exocrine pancreatic cancer in male rats only, but found no chemical that induced pancreatic cancer in female rats only. Furthermore...
Chapter
IntroductionDNA RepairTranscription Elongation and DNA DamageRNA Polymerases: A Brief OverviewRNA Polymerase Elongation Past DNA DamageConclusions AcknowledgementsReferences