Oxidative DNA damage and repair in skeletal muscle of humans exposed to high-altitude hypoxia.
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Oxidative DNA damage and repair in skeletal muscle of humans exposed to high-altitude hypoxia. / Lundby, Carsten; Pilegaard, Henriette; van Hall, Gerrit; Sander, Mikael; Calbet, Jose; Loft, Steffen; Møller, Peter.
In: Toxicology, Vol. 192, No. 2-3, 2003, p. 229-36.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Oxidative DNA damage and repair in skeletal muscle of humans exposed to high-altitude hypoxia.
AU - Lundby, Carsten
AU - Pilegaard, Henriette
AU - van Hall, Gerrit
AU - Sander, Mikael
AU - Calbet, Jose
AU - Loft, Steffen
AU - Møller, Peter
N1 - Keywords: Adaptation, Physiological; Adult; Altitude Sickness; DNA Damage; DNA Repair; Female; Humans; Male; Muscle, Skeletal; Oxidative Stress; Time Factors
PY - 2003
Y1 - 2003
N2 - Recent research suggests that high-altitude hypoxia may serve as a model for prolonged oxidative stress in healthy humans. In this study, we investigated the consequences of prolonged high-altitude hypoxia on the basal level of oxidative damage to nuclear DNA in muscle cells, a major oxygen-consuming tissue. Muscle biopsies from seven healthy humans were obtained at sea level and after 2 and 8 weeks of hypoxia at 4100 m.a.s.l. We found increased levels of strand breaks and endonuclease III-sensitive sites after 2 weeks of hypoxia, whereas oxidative DNA damage detected by formamidopyrimidine DNA glycosylase (FPG) protein was unaltered. The expression of 8-oxoguanine DNA glycosylase 1 (OGG1), determined by quantitative RT-PCR of mRNA levels did not significantly change during high-altitude hypoxia, although the data could not exclude a minor upregulation. The expression of heme oxygenase-1 (HO-1) was unaltered by prolonged hypoxia, in accordance with the notion that HO-1 is an acute stress response protein. In conclusion, our data indicate high-altitude hypoxia may serve as a good model for oxidative stress and that antioxidant genes are not upregulated in muscle tissue by prolonged hypoxia despite increased generation of oxidative DNA damage.
AB - Recent research suggests that high-altitude hypoxia may serve as a model for prolonged oxidative stress in healthy humans. In this study, we investigated the consequences of prolonged high-altitude hypoxia on the basal level of oxidative damage to nuclear DNA in muscle cells, a major oxygen-consuming tissue. Muscle biopsies from seven healthy humans were obtained at sea level and after 2 and 8 weeks of hypoxia at 4100 m.a.s.l. We found increased levels of strand breaks and endonuclease III-sensitive sites after 2 weeks of hypoxia, whereas oxidative DNA damage detected by formamidopyrimidine DNA glycosylase (FPG) protein was unaltered. The expression of 8-oxoguanine DNA glycosylase 1 (OGG1), determined by quantitative RT-PCR of mRNA levels did not significantly change during high-altitude hypoxia, although the data could not exclude a minor upregulation. The expression of heme oxygenase-1 (HO-1) was unaltered by prolonged hypoxia, in accordance with the notion that HO-1 is an acute stress response protein. In conclusion, our data indicate high-altitude hypoxia may serve as a good model for oxidative stress and that antioxidant genes are not upregulated in muscle tissue by prolonged hypoxia despite increased generation of oxidative DNA damage.
M3 - Journal article
C2 - 14580789
VL - 192
SP - 229
EP - 236
JO - Toxicology
JF - Toxicology
SN - 0300-483X
IS - 2-3
ER -
ID: 8442619