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Oxidative DNA damage; assessment and meaning in some human pathologies

Daniel Gackowski ,  Agnieszka B. Siomek ,  Rafał Różalski ,  Marek Foksiński ,  Ryszard S. Oliński 

Nicolaus Copernicus University, Collegium Medicum , Department of Clinical Biochemistry, ul. Karlowicza 24, Bydgoszcz 85-092, Poland

Abstract
Reactive oxygen species (ROS) can cause oxidative damage to DNA which may be a major cause of various diseases such as cancer. Commonly used biomarkers of oxidative DNA damage include measure of 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG) and its corresponding base, 8-oxoguanine. These modifications can be determined either in cellular DNA or in urine where their excretion represents the average rate of oxidative DNA damage in the total body. In order to assess the role of oxidative DNA damage in cancer atherosclerosis and dementia development we decided, for the first time, to analyse the broad spectrum of oxidative DNA damage biomarkers; urinary excretion of the base/nucleoside modification as well as the level of oxidative damage in cellular DNA and repair of the damage.
It has been found that the levels of oxidative DNA damage were significantly higher while the concentrations of the antioxidant vitamins were significantly lower in colon and lung cancer patients than in control group. Moreover, the same direction of the changes has been found in patients with adenoma. This, in turn, suggests that the changes in aforementioned biomarkers of oxidative stress are characteristic for cancer development. It is evident that oxidants act at several stages in the malignant transformation since they can interfere with integrity of the genome. However, the quantitative relationship between the measured DNA damage and the rate of mutation and cancer is still lacking.
The levels of 8-oxodG was significantly higher and vitamin C concentration was significantly lower in the atherosclerotic patients group than in control group. Although increasing number of experimental evidences pointed out that oxidative DNA damage may play a causative role in atherosclerosis it is also clear that the presence of the damage in atherosclerotic plaque may not necessarily be the direct cause of the disease development. It can rather mirror prooxidative conditions of the patients’ blood.
All the parameters which represent oxidative damage to DNA on the level of the whole organism , i.e. urinary excretion of 8-oxoguanine and 8-oxodG and also the level of 8-oxodG in leukocyte’s DNA were higher in patients with mixed dementia than in the control group. Moreover, the concentration of antioxidants in plasma were significantly lower in patients group. It suggest, that simple treatment of these patients with antioxidant vitamins may likely present a strategy for slowing progression of the disease.

Acknowledgment:

This work was supported in part by ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: "Food Quality and Safety" (Contract No 513943), and by grant from the Ministry of Science and Information Society Technologies 2P05D062 27.


 

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Presentation: Wykład at Zjazd Polskiego Towarzystwa Biochemicznego, Sympozjum I, by Daniel Gackowski
See On-line Journal of Zjazd Polskiego Towarzystwa Biochemicznego

Submitted: 2007-05-08 14:51
Revised:   2009-06-07 00:44