Repeated inhalations of diesel exhaust particles and oxidatively damaged DNA in young oxoguanine DNA glycosylase (OGG1) deficient mice.
DNA repair may prevent increased levels of oxidatively damaged DNA from prolonged oxidative stress induced by, e.g. exposure to diesel exhaust particles (DEP). We studied oxidative damage to DNA in broncho-alveolar lavage cells, lungs, and liver after 4 x 1.5 h inhalations of DEP (20 mg/m3) in Ogg1-/- and wild type (WT) mice with similar extent of inflammation. DEP exposure increased lung levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in Ogg1-/- mice, whereas no effect on 8-oxodG or oxidized purines in terms of formamidopyrimidine DNA glycosylase (FPG) sites was observed in WT mice. In both unexposed and exposed Ogg1-/- mice the level of FPG sites in the lungs was 3-fold higher than in WT mice. The high basal level of FPG sites in Ogg1-/- mice probably saturated the assay and prevented detection of DEP-generated damage. In conclusion, Ogg1-/- mice have elevated pulmonary levels of FPG sites and accumulate genomic 8-oxodG after repeated inhalations of DEP.
Risom
Lotte
L
Department of Occupational and Environmental Health, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark. l.risom@pubhealth.ku.dk
Dybdahl
Marianne
M
Møller
Peter
P
Wallin
Håkan
H
Haug
Terje
T
Vogel
Ulla
U
Klungland
Arne
A
Loft
Steffen
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000280:Administration, Inhalation; D000367:Age Factors; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004249:DNA Damage; D045647:DNA Glycosylases / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D004260:DNA Repair / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D043382:DNA-Formamidopyrimidine Glycosylase / Q000494:pharmacology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004720:Endonucleases / Q000096:biosynthesis / Q000235:genetics; D029968:Escherichia coli Proteins / Q000494:pharmacology; D005260:Female; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008168:Lung / Q000737:chemistry / Q000187:drug effects / Q000528:radiation effects; D016676:Macrophages, Alveolar / Q000187:drug effects; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000187:drug effects; D018384:Oxidative Stress; D011759:Pyrrolidines / Q000494:pharmacology; D011807:Quinolizines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D001335:Vehicle Emissions / Q000633:toxicity*
D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D015850:Interleukin-6; D008565:Membrane Proteins; D011759:Pyrrolidines; D011807:Quinolizines; D012333:RNA, Messenger; D001335:Vehicle Emissions; C076809:Ro 19-8022; D000080242:8-Hydroxy-2'-Deoxyguanosine; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D004720:Endonucleases; C499360:Ercc1 protein, mouse; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse; D043382:DNA-Formamidopyrimidine Glycosylase; D003849:Deoxyguanosine