In vivo exposure to hyperoxia induces DNA damage in a population of alveolar type II epithelial cells.
It is well established that hyperoxia injures and kills alveolar endothelial and type I epithelial cells of the lung. Although type II epithelial cells remain morphologically intact, it remains unclear whether they are also damaged. DNA integrity was investigated in adult mice whose type II cells were identified by their endogenous expression of pro-surfactant protein C or transgenic expression of enhanced green fluorescent protein. In mice exposed to room air, punctate perinuclear 8-oxoguanine staining was detected in approximately 4% of all alveolar cells and in 30% of type II cells. After 48 or 72 h of hyperoxia, 8-oxoguanine was detected in 11% of all alveolar cells and in >60% of type II cells. 8-Oxoguanine colocalized by confocal microscopy with the mitochondrial transmembrane protein cytochrome oxidase subunit 1. Type II cells isolated from hyperoxic lungs exhibited nuclear DNA strand breaks by comet assay even though they were viable and morphologically indistinguishable from cells isolated from lungs exposed to room air. These data reveal that type II cells exposed to in vivo hyperoxia have oxidized and fragmented DNA. Because type II cells are essential for lung remodeling, our findings raise the possibility that they are proficient in DNA repair.
Roper
Jason M
JM
Dept. of Pediatrics, Box 850, School of Medicine and Dentistry, Univ. of Rochester, 601 Elmwood Ave., Rochester, NY 14642, USA.
Mazzatti
Dawn J
DJ
Watkins
Richard H
RH
Maniscalco
William M
WM
Keng
Peter C
PC
O'Reilly
Michael A
MA
D000388:Air; D000818:Animals; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000235:genetics; D049452:Green Fluorescent Proteins; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D018496:Hyperoxia / Q000235:genetics / Q000503:physiopathology*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011650:Pulmonary Alveoli / Q000503:physiopathology*; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D020545:Respiratory Mucosa / Q000503:physiopathology*; D013997:Time Factors
D004272:DNA, Mitochondrial; D008164:Luminescent Proteins; D037721:Pulmonary Surfactant-Associated Protein C; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins; C024829:8-hydroxyguanine; D006147:Guanine