X-ray-induced oxidative stress: DNA damage and gene expression of HO-1, ERCC1 and OGG1 in mouse lung.
Effects of X-ray induced oxidative stress in mouse lungs were studied in terms of DNA damage and expression of antioxidant defense and DNA repair genes. Lung samples were collected immediately after, and 3, 6, and 22 h after irradiation with 1, 3, 10 or 30 Gy X-rays of the thorax. The levels of strand breaks (SB), formamidopyrimidine DNA glycosylase (FPG) and endonuclease III (ENDOIII) sensitive sites, detected by the comet assay, were increased dose-dependently immediately after irradiation, whereas 8-oxo-7,8-dihydro-2'-deoxyguanosine analyzed by HPLC-EC was unaltered, possibly due to a relatively high background level (2.5/10(6) dG in control tissue). Complete repair of SB was observed 3 h after irradiation, whereas the period required for repair of ENDOIII and FPG sensitive sites was longer. Determined by RT-PCR, the mRNA expression of heme oxygenase-1 (HO-1) was increased 40-fold 6 h after irradiation, whereas the expression of 8-oxoguanine glycosylase (OGG1) and ERCC1 were increased 2.5-fold 6 h after exposure, with saturation at the lowest dose. In conclusion, this study shows the feasibility of partial-body X-ray irradiation as an in vivo model for induction and repair of oxidative DNA damage, and expression of relevant DNA repair and antioxidant defense genes.
Risom
Lotte
L
Institute of Public Health, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen, Denmark.
Møller
Peter
P
Vogel
Ulla
U
Kristjansen
Paul E G
PE
Loft
Steffen
S
D000818:Animals; D020552:Comet Assay; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins; D004307:Dose-Response Relationship, Radiation; D004720:Endonucleases; D005260:Female; D015870:Gene Expression; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics*; D051547:Heme Oxygenase-1; D008168:Lung / Q000528:radiation effects*; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D004720:Endonucleases; C499360:Ercc1 protein, mouse; D045647:DNA Glycosylases