Hypoxia and oxidation levels of DNA and lipids in humans and animal experimental models

Abstract

SummaryThe objective of this review was to evaluate the association between hypoxia and oxidative damage to DNA and lipids. Evaluation criteria encompassed specificity and validation status of the biomarkers, study design, strength of the association, dose-response relationship, biological plausibility, analogous exposures, and effect modification by intervention. The collective interpretation indicates persuasive evidence from the studies in humans for an association between hypoxia and elevated levels of oxidative damage to DNA and lipids. The levels of oxidatively generated DNA lesions and lipid peroxidation products depend on both the duration and severity of the exposure to hypoxia. Largest effects are observed with exposure to hypoxia at high altitude, but other factors, including ultraviolet light, exercise, exertion, and low intake of antioxidants, might contribute to the effect observed in subjects at high altitude. Most of the animal experimental models should be interpreted with caution because the assays for assessment of lipid peroxidation products have suboptimal validity.2008 IUBMB IUBMB Life, 60(11): 707-723, 2008

Oxidative Damage to DNA and Lipids as Biomarkers of Exposure to Air Pollution

“…The level of oxidatively damaged DNA measured by the comet assay in WBCs of humans is < 1 lesion/10 6 nucleotides (Møller 2006). Oxidatively damaged DNA, nucleobases, and LPO products can be measured by antibody-based methods, but artificially high background levels can occur because of unspecific binding of the antibodies to other biomolecules (Halliwell and Whiteman 2004; Møller et al 2008b). The simple assay of TBARS and CDs has been seriously criticized and is not recommended for in vivo detection of LPO products, whereas improved methods using high-performance liquid chromatography (HPLC) purification steps are more reliable assays of TBARS (Halliwell and Whiteman 2004).…”

Antioxidant defense and oxidative damage vary widely among high‐altitude residents

“…Relative oxygen scarcity results in a partial reduction to super-oxide and hydrogen peroxide. Reactive oxygen species (ROS) can damage intracellular biomolecules, including DNA (Cash, Pan, & Simon, 2007; Klimova & Chandel, 2008; Moller, Risom, Lundby, Mikkelsen, & Loft, 2008; Schumacker, 2011); however, they are necessary for initiating transcription of loci underlying adaptive responses such as erythropoietin synthesis (Simon, 2006). Cells defend against ROS by upregulating antioxidants, primarily the powerful superoxide dismutases (SOD) (Comhair & Erzurum, 2010).…”

“…Shorter-term, multigenerational populations include the Oromo, also in Ethiopia, who have lived at altitude for ~500 years (Beall, 2014). Our understanding of the antioxidant response in high-altitude populations is incomplete due to limitations in samples and measures selected, and variation in the genetic background of populations, altitudes, and length of exposure (Moller et al, 2008). …”

Cerebrospinal Fluid Oxidative Stress During Chemotherapy of Acute Lymphoblastic Leukemia in Children

“…However, an excessive oxidative stress may result in DNA, lipid, and protein damage, leading to cell injury. In oncology, reactive oxygen species (ROS) play a dual role, they may cause DNA damage and carcinogenesis [9], but may also increase the therapeutic potential of anticancer agents [10].…”