title: Triggering Mechanisms and Inflammatory Effects of Combustion Exhaust Particles with Implication for Carcinogenesis.
abstract: 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.
authors.affiliation: Department of Air Pollution and Noise, Domain for Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Johan
authors.initials: J
authors.lastname: Øvrevik
authors.affiliation: Department of Air Pollution and Noise, Domain for Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Magne
authors.initials: M
authors.lastname: Refsnes
authors.affiliation: Department of Air Pollution and Noise, Domain for Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Marit
authors.initials: M
authors.lastname: Låg
authors.affiliation: Department of Air Pollution and Noise, Domain for Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Bendik C
authors.initials: BC
authors.lastname: Brinchmann
authors.affiliation: Department of Air Pollution and Noise, Domain for Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Per E
authors.initials: PE
authors.lastname: Schwarze
authors.affiliation: Department of Air Pollution and Noise, Domain for Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Jørn A
authors.initials: JA
authors.lastname: Holme
mesh_terms: D063646:Carcinogenesis / Q000139:chemically induced*; D002462:Cell Membrane / Q000378:metabolism; D004249:DNA Damage; D004847:Epithelial Cells / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000150:complications; D007473:Ion Channels / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000473:pathology; D018384:Oxidative Stress; D052638:Particulate Matter / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D007473:Ion Channels; D052638:Particulate Matter; D017382:Reactive Oxygen Species; D018336:Receptors, Aryl Hydrocarbon; D011956:Receptors, Cell Surface; D001335:Vehicle Emissions