TY - JOUR
T1 - Repeated inhalations of diesel exhaust particles and oxidatively damaged DNA in young oxoguanine DNA glycosylase (OGG1) deficient mice
AU - Risom, L.
AU - Dybdahl, M.
AU - Møller, P.
AU - Wallin, H.
AU - Haug, T.
AU - Vogel, Ulla Birgitte
AU - Klungland, A.
AU - Loft, S.
PY - 2007
Y1 - 2007
N2 - 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/m(3)) in Qgg1 -/- 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 formamiclopyrimidine DNA glycosylase (FPG) sites was observed in WIT mice. In both unexposed and exposed Qgg1 -/- 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 Qgg1 -/- mice probably saturated the assay and prevented detection of DEP-generated damage. In conclusion, Qgg1 -/- mice have elevated pulmonary levels of FPG sites and accumulate genomic 8-oxodG after repeated inhalations of DEP.
AB - 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/m(3)) in Qgg1 -/- 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 formamiclopyrimidine DNA glycosylase (FPG) sites was observed in WIT mice. In both unexposed and exposed Qgg1 -/- 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 Qgg1 -/- mice probably saturated the assay and prevented detection of DEP-generated damage. In conclusion, Qgg1 -/- mice have elevated pulmonary levels of FPG sites and accumulate genomic 8-oxodG after repeated inhalations of DEP.
U2 - 10.1080/10715760601024122
DO - 10.1080/10715760601024122
M3 - Journal article
SN - 1071-5762
VL - 41
SP - 172
EP - 181
JO - Free Radical Research
JF - Free Radical Research
IS - 2
ER -