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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 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. We have also found that non-dioxin like polychlorinated biphenyls (PCBs) interact with PAH-induced DNA-damage signalling. 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 Prof. Roger Westerholm at the Department of Analytical Chemistry, Stockholm University, Dr. Staffan Lundstedt at the Department of Chemistry, Umeå University and Prof Gisela de Aragão Umbuzeiro at UNICAMP, Limeira, Brazil.

Contact persons

Ulla Stenius, Professor and Kristian Dreij, Associate Professor

Financing

  • Cancer and Allergy foundation
  • Seventh framework program Marie Curie International Re-integration Grants (IRG)
  • Stockholm City Department of Environment
  • Swedish Research Council FORMAS
  • ÅForsk foundation

Publications

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

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Nanomolar levels of PAHs in extracts from urban air induce MAPK signaling in HepG2 cells.
Jarvis I, Bergvall C, Morales D, Kummrow F, Umbuzeiro G, Westerholm R, et al
Toxicol. Lett. 2014 Aug;229(1):25-32  

Interactions between polycyclic aromatic hydrocarbons in complex mixtures and implications for cancer risk assessment.
Jarvis I, Dreij K, Mattsson �, 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 

γH2AX, pChk1, and Wip1 as potential markers of persistent DNA damage derived from dibenzo[a,l]pyrene and PAH-containing extracts from contaminated soils.
Niziolek-Kierecka M, Dreij K, Lundstedt S, Stenius U
Chem. Res. Toxicol. 2012 Apr;25(4):862-72

Non-dioxin-like PCBs interact with benzo[a]pyrene-induced p53-responses and inhibit apoptosis.
Al-Anati L, Högberg J, Stenius U
Toxicol. Appl. Pharmacol. 2010 Dec;249(2):166-77