%0 Journal Article %A Erika Gonzalez %A Juan Henao %A Florian Schelter %A Markus Mueller %A Xin Zhang %A Thomas Carell %A Benjamin Schubert %A Anne Hilgendorff %T Late Breaking Abstract - Short exposure to moderate hyperoxia leads to long term effects in the murine lung in-vivo %D 2021 %R 10.1183/13993003.congress-2021.OA1617 %J European Respiratory Journal %P OA1617 %V 58 %N suppl 65 %X Background: Preterm newborns often require life-saving oxygen therapy. Prolonged treatment with severe hyperoxia (FiO2>0.6) leads to irreversible changes in the developing lung. However, the effects of clinically relevant levels of hyperoxia i.e. moderate hyperoxia (FiO2=0.4) remain understudied. Here, we aimed to study how short-term moderate hyperoxia treatment alters the developing lung long term.Methods: In vivo, 5-7 C57BL/6 day-old mice were treated with moderate hyperoxia (FiO2=0.4) or RA (FiO2=0.21) for 8 hours. Half the mice were sacrificed (baseline) while the rest were returned to their mothers and allowed to grow for 18 months (long-term). Lungs were harvested for methylation analysis and protein expression.Results: Although no changes were found at baseline, Pdgfra and Ve-cadherin protein expressions were downregulated long-term in mice treated with FiO2=0.4. Following FiO2=0.4 treatment, pRb protein and pMcm2 were downregulated at baseline indicating cell-cycle arrest. Moreover, in methylation analysis, we observed differences in the content of DNA methylated bases (hmC, fC, caC), and 8-oxoguanine (DNA oxidative lesion) at baseline, an effect that worsened long term. This finding points to alterations in DNA-repair pathways.Conclusions: Moderate hyperoxia leads to long-term lung epigenetic effects in mice in-vivo. The alterations in methylation patterns together with the cell-cycle arrest at baseline imply that short-term moderate hyperoxia leads to long-term changes in DNA-repair pathways, an effect that worsens over time. This argues that short-term moderate hyperoxia treatment could prime the developing lung to a second-hit injury.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, OA1617.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). %U