Elsevier

Free Radical Biology and Medicine

Volume 47, Issue 8, 15 October 2009, Pages 1230-1233
Free Radical Biology and Medicine

Original Contribution
Urinary excretion of biomarkers of oxidatively damaged DNA and RNA in hereditary hemochromatosis

https://doi.org/10.1016/j.freeradbiomed.2009.08.004Get rights and content

Abstract

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.

Section snippets

Material and methods

The study design has been described in detail elsewhere [1]. In brief, urine samples were collected from 21 newly diagnosed untreated cases with hereditary hemochromatosis and 21 controls, and blood samples were secured for analysis of iron status. Liver iron concentration and non-transferrin-bound iron were quantified in patients only [1]. All patients were HFE C282Y homozygotes. Spot urine samples were collected from controls and from the patients before the latter underwent treatment with

Results

At baseline the urinary excretion of the RNA oxidation product 8-oxoGuo was 2.5-fold increased in patients with hereditary hemochromatosis (P = 0.006) compared with controls (Table 1). There were no significant differences in the excretion of the DNA oxidation product (8-oxodGuo) or the oxidized base (8-oxoGua).

After treatment of the patients with phlebotomy, the excretion of both the DNA and the RNA oxidation products was reduced significantly (Table 2). The excretion of the RNA oxidation

Discussion

In this study we show a 2.5-fold increase in RNA oxidation, measured as excretion of 8-oxoGuo in HFE C282Y homozygous patients compared with controls. Interestingly, the DNA oxidation measured as excretion of 8-oxodGuo did not differ between hemochromatosis patients and controls. However, after treatment of the hemochromatosis patients until normalization of their iron parameters, both RNA and DNA oxidation were reduced—the DNA oxidation by 30% and the RNA oxidation to one-third of the values

Acknowledgment

This study was supported by research funding from the Research Committee at Copenhagen University Hospital–Rigshospitalet.

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