Urinary excretion of biomarkers of oxidatively damaged DNA and RNA in hereditary hemochromatosis.
Oxidatively generated damage to nucleic acids is considered to play a significant role in carcinogenesis, and it has been shown that people with hereditary hemochromatosis are at increased risk of cancer. In this study we used a new refined liquid chromatography-tandem mass spectrometry method to measure the urinary excretion of oxidatively generated 8-oxo-7,8-dihydroguanine and related 2'-deoxyribonucleoside and ribonucleoside derivatives in hereditary hemochromatosis patients, and we investigated the effect of treatment on the levels of these modifications. The study was carried out as a classical case-control study of 21 newly diagnosed, never treated hereditary hemochromatosis patients and 21 matched controls. We found that at baseline the urinary excretion of the RNA oxidation product 8-oxo-7,8-dihydroguanosine (8-oxoGuo) was 2.5-fold increased in patients compared with controls, and after phlebotomy treatment the excretion of the RNA oxidation product 8-oxoGuo returned to control values and the excretion of the DNA product 8-oxo-7,8-dihydro-2'-deoxyguanosine was reduced by 30%. In patients with hereditary hemochromatosis oxidative stress on nucleic acids is an important feature of the iron overload seen in this disease. By this mechanism cellular damage resulting in end organ damage, typically seen in the liver of such patients, may be mediated.
Broedbaek
Kasper
K
Laboratory of Clinical Pharmacology Q7642, Rigshospitalet, DK-2200 Copenhagen, Denmark. kasper.broedbaek@rh.regionh.dk
Poulsen
Henrik E
HE
Weimann
Allan
A
Kom
Ghainsom D
GD
Schwedhelm
Edzard
E
Nielsen
Peter
P
Böger
Rainer H
RH
D000080242:8-Hydroxy-2'-Deoxyguanosine; D015415:Biomarkers / Q000652:urine*; D016022:Case-Control Studies; D004249:DNA Damage / Q000235:genetics*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D005293:Ferritins / Q000097:blood; D006432:Hemochromatosis / Q000235:genetics* / Q000652:urine*; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012313:RNA / Q000235:genetics*; D053719:Tandem Mass Spectrometry
D015415:Biomarkers; C075750:8-epi-prostaglandin F2alpha; D012313:RNA; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005293:Ferritins; D015237:Dinoprost; D003849:Deoxyguanosine