Repeated inhalations of diesel exhaust particles and oxidatively damaged DNA in young oxoguanine DNA glycosylase (OGG1) deficient mice |
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| Authors: | Risom Lotte Dybdahl Marianne Møller Peter Wallin Håkan Haug Terje Vogel Ulla Klungland Arne Loft Steffen |
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| Affiliation: | a Department of Occupational and Environmental Health, Institute of Public Health, University of Copenhagen, Copenhagen, Denmarkb National Institute of Occupational Health, Copenhagen, Denmarkc Center for Occupational and Environmental Medicine, The National Hospital, Oslo, Norwayd Institute of Medical Microbiology, The National Hospital, Oslo, Norway |
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| Abstract: | 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 × 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. |
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| Keywords: | Oxidative stress DNA repair 8-oxodG OGG1 comet assay diesel exhaust particles |
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