Oxidative stress and inflammation generated DNA damage by exposure to air pollution particles

Peter Møller, Pernille Høgh Danielsen, Dorina Gabriela Karottki, Kim Jantzen, Martin Roursgaard, Henrik Klingberg, Ditte Marie Jensen, Daniel Vest Christophersen, Jette Gjerke Hemmingsen, Yi Cao, Steffen Loft

Research output: Contribution to journalReviewResearchpeer-review

272 Citations (Scopus)

Abstract

Generation of oxidatively damaged DNA by particulate matter (PM) is hypothesized to occur via production of reactive oxygen species (ROS) and inflammation. We investigated this hypothesis by comparing ROS production, inflammation and oxidatively damaged DNA in different experimental systems investigating air pollution particles. There is substantial evidence indicating that exposure to air pollution particles was associated with elevated levels of oxidatively damaged nucleobases in circulating blood cells and urine from humans, which is supported by observations of elevated levels of genotoxicity in cultured cells exposed to similar PM. Inflammation is most pronounced in cultured cells and animal models, whereas an elevated level of oxidatively damaged DNA is more pronounced than inflammation in humans. There is non-congruent data showing corresponding variability in effect related to PM sampled at different locations (spatial variability), times (temporal variability) or particle size fraction across different experimental systems of acellular conditions, cultured cells, animals and humans. Nevertheless, there is substantial variation in the genotoxic, inflammation and oxidative stress potential of PM sampled at different locations or times. Small air pollution particles did not appear more hazardous than larger particles, which is consistent with the notion that constituents such as metals and organic compounds also are important determinants for PM-generated oxidative stress and inflammation. In addition, the results indicate that PM-mediated ROS production is involved in the generation of inflammation and activated inflammatory cells can increase their ROS production. The observations indicate that air pollution particles generate oxidatively damaged DNA by promoting a milieu of oxidative stress and inflammation.

Original languageEnglish
JournalMutation Research - Reviews
Volume762
Pages (from-to)133-166
Number of pages34
ISSN1383-5742
DOIs
Publication statusPublished - 2014

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