Project: Interactions between PAHs in complex mixtures and toxicological effects

The methods commonly used for assessing the toxicity of complex environmental mixtures probably significantly underestimate the risk of exposure to human health since they do not take into account interactions which potentially give rise to synergistic effects. Our aim is to improve the risk assessment of complex environmental mixtures.

One major group of environmental pollutants is the polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene and dibenzo[a,l]pyrene, which have been linked with numerous adverse health effects including cancer, cardiovascular and respiratory diseases, developmental effects, premature mortality and increased infant mortality. The goal of this project is to investigate the harmful effects of exposure to complex 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 effects of complex mixtures of PAHs in environmental samples on DNA damage and repair, inflammation and development. Samples are obtained from urban and biomass burning air particulate matter and soil collected at urban as well as industrial locations. The test systems we use are human cell lines and zebrafish (Danio rerio) embryos.

Our published data indicate that complex environmental PAH mixtures induce unexpected and persistent DNA damage signalling responses. We also show that the more polar PAHs, including the oxygenated PAHs, exert significant biological activity and should thus be included in the risk assessment. Our hypothesis is that synergistic effects between different PAHs and other pollutants in complex mixtures represent a major carcinogenic effect and there is an urgent need to include these interactions in health risk assessment.

In this project we collaborate with Dr. Ioannis Sadiktsis at Stockholm University, Prof Gisela de Aragão Umbuzeiro at UNICAMP, Limeira, Brazil, and Prof Silvia Batistuzzo at UFRN, Natal, Brazil.

Financing

  • Cancer and Allergy foundation
  • Stockholm City Department of Environment
  • Swedish Environmental Protection Agency
  • Swedish Research Council FORMAS
  • STINT/CAPES

Publications

Determination of whole mixture-based potency factors for cancer risk assessment of complex environmental mixtures by in vitro testing of standard reference materials.
de Oliveira Galvão MF, Sadiktsis I, Marques Pedro T, Dreij K
Environ Int 2022 Jun;166():107345

Polycyclic aromatic compounds in particulate matter and indoor dust at preschools in Stockholm, Sweden: Occurrence, sources and genotoxic potential in vitro.
Lim H, Sadiktsis I, de Oliveira Galvão MF, Westerholm R, Dreij K
Sci Total Environ. 2021 Feb 10;755(Pt 1):142709

Mixture effects of oxygenated PAHs and benzo[a]pyrene on cardiovascular development and function in zebrafish embryos.
Cunha V, Vogs C, Le Bihanic F, Dreij K
Environ Int 2020 Jun;143():105913

Similar polycyclic aromatic hydrocarbon and genotoxicity profiles of atmospheric particulate matter from cities on three different continents.
Maselli BS, Cunha V, Lim H, Bergvall C, Westerholm R, Dreij K, et al
Environ. Mol. Mutagen. 2020 Jun;61(5):560-573

Polycyclic aromatic compounds in urban soils of Stockholm City: Occurrence, sources and human health risk assessment.
Dreij K, Lundin L, Le Bihanic F, Lundstedt S
Environ. Res. 2020 Mar;182():108989

Genotoxicity and DNA damage signaling in response to complex mixtures of PAHs in biomass burning particulate matter from cashew nut roasting.
de Oliveira Galvão MF, Sadiktsis I, Batistuzzo de Medeiros SR, Dreij K
Environ. Pollut. 2019 Oct;():113381

Comparative mutagenic activity of atmospheric particulate matter from Limeira, Stockholm, and Kyoto.
Maselli BS, Giron MCG, Lim H, Bergvall C, Westerholm R, Dreij K, et al
Environ. Mol. Mutagen. 2019 08;60(7):607-616

In vitro and in vivo genotoxicity of oxygenated polycyclic aromatic hydrocarbons.
McCarrick S, Cunha V, Zapletal O, Vondráček J, Dreij K
Environ. Pollut. 2019 Mar;246():678-687

Cancer Risk Assessment of Airborne PAHs Based on in Vitro Mixture Potency Factors.
Dreij K, Mattsson Å, Jarvis IWH, Lim H, Hurkmans J, Gustafsson J, et al
Environ. Sci. Technol. 2017 Aug;51(15):8805-8814

Aryl hydrocarbon receptor activation and developmental toxicity in zebrafish in response to soil extracts containing unsubstituted and oxygenated PAHs.
Wincent E, Jönsson ME, Bottai M, Lundstedt S, Dreij K
Environ. Sci. Technol. 2015 Mar;49(6):3869-77

Detection of benz[j]aceanthrylene in urban air and evaluation of its genotoxic potential.
Lim H, Mattsson Å, Jarvis IW, Bergvall C, Bottai M, Morales DA, et al
Environ. Sci. Technol. 2015 Mar;49(5):3101-9

Interactions between polycyclic aromatic hydrocarbons in complex mixtures and implications for cancer risk assessment.
Jarvis I, Dreij K, Mattsson Å, Jernström B, Stenius U
Toxicology 2014 Jul;321():27-39

Sensitivity of Salmonella YG5161 for detecting PAH-associated mutagenicity in air particulate matter.
Umbuzeiro G, Kummrow F, Morales D, Alves D, Lim H, Jarvis I, et al
Environ. Mol. Mutagen. 2014 Jul;55(6):510-7

Persistent activation of DNA damage signaling in response to complex mixtures of PAHs in air particulate matter.
Jarvis I, Bergvall C, Bottai M, Westerholm R, Stenius U, Dreij K
Toxicol. Appl. Pharmacol. 2013 Feb;266(3):408-18 

Contact persons

Profile image

Kristian Dreij

Principal Investigator
AP
Content reviewer:
Anna Persson
08-03-2024