title: Hydroxyl-radical-dependent DNA damage by ambient particulate matter from contrasting sampling locations.
abstract: Exposure to ambient particulate matter (PM) has been reported to be associated with increased respiratory, cardiovascular, and malignant lung disease. Previously we have shown that PM can induce oxidative DNA damage in A549 human lung epithelial cells. The aims of the present study were to investigate the variability of the DNA-damaging properties of PM sampled at different locations and times and to relate the observed effects to the hydroxyl-radical (OH)-generating activities of these samples. Weekly samples of coarse (10-2.5 microm) and fine (<2.5 microm) PM from four sites (Nordrheim Westfalen, Germany) were analyzed for hydrogen-peroxide-dependent OH formation using electron paramagnetic resonance and formation of 8-hydroxydeoxyguanosine (8-OHdG) in calf thymus DNA using an immuno-dot-blot assay. DNA strand breakage by fine PM in A549 human lung epithelial cells was quantified using the alkaline comet assay. Both PM size distribution fractions elicited OH generation and 8-OHdG formations in calf thymus DNA. Significantly higher OH generation was observed for PM sampled at urban/industrial locations and for coarse PM. Samples of fine PM also caused DNA strand breakage in A549 cells and this damage could be prevented using the hydroxyl-radical scavengers 5,5-dimethyl-1-pyrroline-N-oxide and dimethyl sulfoxide. The observed DNA strand breakage appeared to correlate with the hydroxyl-radical-generating capacities of the PM samples but with different profiles for rural versus urban/industrial samples. In conclusion, when considered at equal mass, OH formation of PM shows considerable variability with regard to the sampling location and time and is correlated with its ability to cause DNA damage.
authors.affiliation: Institut für Umweltmedizinische Forschung an der Heinrich-Heine University Düsseldorf gGmbH, auf'm Hennekamp 50, D-40225 Düsseldorf, Germany.
authors.forename: Tingming
authors.initials: T
authors.lastname: Shi
authors.forename: Rodger
authors.initials: R
authors.lastname: Duffin
authors.forename: Paul J A
authors.initials: PJ
authors.lastname: Borm
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Christel
authors.initials: C
authors.lastname: Weishaupt
authors.forename: Roel P F
authors.initials: RP
authors.lastname: Schins
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000393:Air Pollutants / Q000032:analysis / Q000633:toxicity*; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004391:Dust / Q000032:analysis; D004578:Electron Spin Resonance Spectroscopy; D004784:Environmental Monitoring; D005858:Germany; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism*; D010316:Particle Size
chemical_list: D000393:Air Pollutants; D004391:Dust; D017665:Hydroxyl Radical; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; C427203:calf thymus DNA; D003849:Deoxyguanosine