Acute hypoxia and reoxygenation-induced DNA oxidation in human mononuclear blood cells.
Research indicates that exposure to hypoxia is associated with oxidative stress. In this investigation, healthy subjects were exposed to hypoxia by inhalation of 10% oxygen for 2h (corresponding to 5500m above sea level). The levels of strand breaks and oxidatively damaged purine bases, measured by the comet assay, and the expression of genes involved in DNA repair of oxidatively damaged DNA were investigated in mononuclear blood cells (MNBC) at baseline, after 2h of hypoxia, 2h of reoxygenation, and 1 day and 8 days after the exposure. The level of strand breaks and oxidized purine bases in MNBC increased following both the 2h of hypoxia and the 2h reoxygenation period, whereas this effect was not observed in unexposed subjects. The expressions of oxoguanine DNA glycosylase 1 (OGG1), nucleoside diphosphate linked moiety X-type motif 1 (NUDT1), nei endonuclease VIII-like 1 (NEIL1), and mutY homolog (MUTYH) were unaltered throughout the experiment in both groups of subjects, indicating that DNA repair genes are not up-regulated by the hypoxia and reoxygenation treatment. Taken together, this report shows that inhalation of 10% oxygen for 2h is associated with increased number of oxidized DNA lesions in MNBC, but acute hypoxia may not inflict upon the regulation of genes involved in repair of oxidized DNA.
Risom
Lotte
L
Institute of Public Health, University of Copenhagen, Øster Farimagsgade 5A, Postbox 2099, DK-1014 Copenhagen K, Denmark.
Lundby
Carsten
C
Thomsen
Jonas Juhl
JJ
Mikkelsen
Lone
L
Loft
Steffen
S
Friis
Gitte
G
Møller
Peter
P
D000328:Adult; D001483:Base Sequence; D020552:Comet Assay; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D000860:Hypoxia / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics
D017931:DNA Primers; D012333:RNA, Messenger; D010744:Phosphoric Monoester Hydrolases; D045647:DNA Glycosylases; C473634:NEIL1 protein, human; C061738:mutY adenine glycosylase; C479058:oxoguanine glycosylase 1, human; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes