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Triggering Mechanisms and Inflammatory Effects of Combustion Exhaust Particles with Implication for Carcinogenesis
Author(s) -
Øvrevik Johan,
Refsnes Magne,
Låg Marit,
Brinchmann Bendik C.,
Schwarze Per E.,
Holme Jørn A.
Publication year - 2017
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12746
Subject(s) - aryl hydrocarbon receptor , inflammation , reactive oxygen species , chemokine , carcinogenesis , microbiology and biotechnology , oxidative stress , dna damage , chemistry , receptor , immune system , proinflammatory cytokine , cytokine , immunology , biology , biochemistry , dna , transcription factor , gene
A number of biological responses may contribute to the carcinogenic effects of combustion‐derived particulate matter ( CPM ). Here, we focus on mechanisms that trigger CPM ‐induced pro‐inflammatory responses. Inflammation has both genotoxic and non‐genotoxic implications and is considered to play a central role in development of various health outcome associated with CPM exposure, including cancer. Chronic, low‐grade inflammation may cause DNA damage through a persistent increased level of reactive oxygen species ( ROS ) produced and released by activated immune cells. Moreover, a number of pro‐inflammatory cytokines and chemokines display mitogenic, motogenic, morphogenic and/or angiogenic properties and may therefore contribute to tumour growth and metastasis. The key triggering events involved in activation of pro‐inflammatory responses by CPM and soluble CPM components can be categorized into (i) formation of ROS and oxidative stress, (ii) interaction with the lipid layer of cellular membranes, (iii) activation of receptors, ion channels and transporters on the cell surface and (iv) interactions with intracellular molecular targets including receptors such as the aryl hydrocarbon receptor (AhR). In particular, we will elucidate the effects of diesel exhaust particles ( DEP ) using human lung epithelial cells as a model system.