Oxidative stress-induced DNA damage by particulate air pollution.
Exposure to ambient air particulate matter (PM) is associated with pulmonary and cardiovascular diseases and cancer. The mechanisms of PM-induced health effects are believed to involve inflammation and oxidative stress. The oxidative stress mediated by PM may arise from direct generation of reactive oxygen species from the surface of particles, soluble compounds such as transition metals or organic compounds, altered function of mitochondria or NADPH-oxidase, and activation of inflammatory cells capable of generating ROS and reactive nitrogen species. Resulting oxidative DNA damage may be implicated in cancer risk and may serve as marker for oxidative stress relevant for other ailments caused by particulate air pollution. There is overwhelming evidence from animal experimental models, cell culture experiments, and cell free systems that exposure to diesel exhaust and diesel exhaust particles causes oxidative DNA damage. Similarly, various preparations of ambient air PM induce oxidative DNA damage in in vitro systems, whereas in vivo studies are scarce. Studies with various model/surrogate particle preparations, such as carbon black, suggest that the surface area is the most important determinant of effect for ultrafine particles (diameter less than 100 nm), whereas chemical composition may be more important for larger particles. The knowledge concerning mechanisms of action of PM has prompted the use of markers of oxidative stress and DNA damage for human biomonitoring in relation to ambient air. By means of personal monitoring and biomarkers a few studies have attempted to characterize individual exposure, explore mechanisms and identify significant sources to size fractions of ambient air PM with respect to relevant biological effects. In these studies guanine oxidation in DNA has been correlated with exposure to PM(2.5) and ultrafine particles outdoor and indoor. Oxidative stress-induced DNA damage appears to an important mechanism of action of urban particulate air pollution. Related biomarkers and personal monitoring may be useful tools for risk characterization.
Risom
Lotte
L
Institute of Public Health, University of Copenhagen, Øster Farimagsgade 5, 1014 Copenhagen K, Denmark.
Møller
Peter
P
Loft
Steffen
S
D000397:Air Pollution / Q000009:adverse effects*; D004249:DNA Damage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008171:Lung Diseases / Q000209:etiology / Q000235:genetics; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics; D008670:Metals / Q000633:toxicity; D018384:Oxidative Stress; D017382:Reactive Oxygen Species
D008670:Metals; D017382:Reactive Oxygen Species