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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.
| Abbreviations | ||
| 8-oxodG | = | 8-oxo-7,8-dihydro-2′-deoxyguanosine |
| 8-oxoGua | = | 8-oxo-7,8-dihydroguanine |
| BAL | = | broncho-alveolar lavage |
| BER | = | base excision repair |
| DEP | = | diesel exhaust particle |
| ERCC1 | = | excision repair cross-complementing 1 |
| ESCODD | = | European Standards Committee on Oxidative DNA Damage |
| FPG | = | formamidopyrimidine DNA glycosylase |
| GLM | = | general linear model |
| HO-1 | = | heme oxygenase 1 |
| HPLC-EC | = | high performance liquid chromatography-electrochemical |
| IL-6 | = | interleukin 6 |
| LSD | = | least significant difference |
| NER | = | nucleotide excision repair |
| OGG1 | = | oxoguanine DNA glycosylase |
| ROS | = | reactive oxygen species |
| SB | = | strand breaks |
| SRM | = | standard reference material |
| Abbreviations | ||
| 8-oxodG | = | 8-oxo-7,8-dihydro-2′-deoxyguanosine |
| 8-oxoGua | = | 8-oxo-7,8-dihydroguanine |
| BAL | = | broncho-alveolar lavage |
| BER | = | base excision repair |
| DEP | = | diesel exhaust particle |
| ERCC1 | = | excision repair cross-complementing 1 |
| ESCODD | = | European Standards Committee on Oxidative DNA Damage |
| FPG | = | formamidopyrimidine DNA glycosylase |
| GLM | = | general linear model |
| HO-1 | = | heme oxygenase 1 |
| HPLC-EC | = | high performance liquid chromatography-electrochemical |
| IL-6 | = | interleukin 6 |
| LSD | = | least significant difference |
| NER | = | nucleotide excision repair |
| OGG1 | = | oxoguanine DNA glycosylase |
| ROS | = | reactive oxygen species |
| SB | = | strand breaks |
| SRM | = | standard reference material |