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1 Department of Pediatrics, Duke University Medical Center, Durham, NC, USA; Department of Cell Biology, Duke University Medical Center, Durham, NC, USA
2 Department of Pediatrics, University of Rochester, Rochester, NY, USA; Environmental Medicine, University of Rochester, Rochester, NY, USA
3 Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA
4 Department of Pediatrics, Duke University Medical Center, Durham, NC, USA
* To whom correspondence should be addressed. E-mail: auten{at}duke.edu.
Transgenic (TG) human (h) EC-SOD targeted to type II cells protects post-natal newborn mouse lung development against hyperoxia by unknown mechanisms. Since alveolar development depends on timely proliferation of type II epithelium and differentiation to type I epithelium, we measured proliferation in bronchiolar and alveolar (SP-C positive) epithelium in air and 95%O2-exposed wild-type (WT) and TG-hEC-SOD newborn mice at post-natal (P) days 3, 5, and 7, traversing the transition from saccular to alveolar stages. We found that TG hEC-SOD ameliorated the 95%O2-impaired BrdU uptake in alveolar and bronchiolar epithelium at P3, but not at P5 and P7 when overall epithelial proliferation rates were lower in air-exposed WT mice. Mouse EC-, CuZn- and Mn-SOD expression were unaffected by hyperoxia or genotype. TG mice had less DNA damage than 95%O2-exposed WT mice at P3, measured by terminal transferase nick-end labeling (TUNEL), p<.05. Hyperoxia induced cell-cycle inhibitory protein p21cip/waf mRNA at P3, WT > TG, p=.06. 95%O2 impaired apical expression of type I cell 
protein (T1, in WT but not in TG mice at P3 and increased T1 in WT and TG mice at P7. Reducing the 95%O2-induced impairment of epithelial proliferation at a critical window of lung development was associated with protection against DNA damage and preservation of apical T1 expression at P3.
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