Increased oxidative damage to DNA in ALS patients

• Published in: Free radical biology & medicine 2000-10, Vol.29 (7), p.652-658
• Main Authors: Bogdanov, Mikhail, Brown, Robert H, Matson, Wayne, Smart, Ryan, Hayden, Doug, O’Donnell, Heather, Flint Beal, M, Cudkowicz, Merit
• Format: Article
• Language: English
• Subjects: 8-Hydroxy-2′-deoxyguanosine; Age of Onset; Amyotrophic lateral sclerosis; Biomarkers - blood; Biomarkers - cerebrospinal fluid; Biomarkers - urine; Cerebrospinal fluid; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - blood; Deoxyguanosine - cerebrospinal fluid; Deoxyguanosine - urine; DNA; DNA Damage; Female; Free radicals; Humans; Male; Middle Aged; Motor Neuron Disease - cerebrospinal fluid; Motor Neuron Disease - metabolism; Motor Neuron Disease - urine; Nervous System Diseases - cerebrospinal fluid; Nervous System Diseases - metabolism; Nervous System Diseases - urine; Plasma; Reference Values; Regression Analysis; Urine
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/S0891-5849(00)00349-X

Although the cause of amyotrophic lateral sclerosis (ALS) is unknown, substantial evidence indicates that oxidative toxicity is associated with neuronal death in this disease. We examined levels of a well-established marker of oxidative damage to DNA, 8-hydroxy-2′-deoxyguanosine (8OH2′dG) in plasma, urine, and cerebrospinal fluid (CSF) at a single time point from subjects with ALS, other neurological diseases, or no known disorders. We also measured the rate of change of 8OH2′dG levels in plasma and urine from ALS and in urine from control subjects over 9 months and examined the relationship to disease severity. In each fluid, 8OH2′dG levels were significantly elevated in the ALS group as compared to control subjects. In all subjects, the plasma and CSF 8OH2′dG levels increased with age, providing further evidence for a role of oxidative damage in normal aging. Plasma and urine 8OH2′dG levels increased significantly with time in the ALS group only. The rate of increase in urine 8OH2′dG levels with time was significantly correlated with disease severity. These findings are consistent with the hypothesis that oxidative pathology accompanies the neurodegenerative process in ALS and suggest that 8OH2′dG may provide a useful tool for monitoring therapeutic interventions in this disease.