Oxidative DNA Damage - the possible use of biomarkers as additional prognostic factors in oncology

Abstract

Oxidative stress represents a deregulation of the homeostasis between the reactive oxygen species and the mechanisms of detoxification and repair. By analyzing the level of oxidatively damaged DNA bases and nucleosides in urine we can assess the extent of DNA repair within the whole body. High levels of markers of oxidative DNA damage excreted in the urine indicate elevated levels of oxidative stress, but can also reflect a high level of efficiency of the processes that work to repair this damage (oxidative stress can be high and the repair processes eliminate its effects). In the present review we discuss the role of oxidative stress, oxidative DNA damage repair mechanisms, potential sources of 8-oxoGua and 8-oxodG (basic markers of oxidative stress) content in urine, effect of antioxidant supplementation on the levels of oxidative DNA lesions, potential application of oxidative DNA damage determination in clinical practice.

Daily hydroxyl radical scavenging capacity of mammals

“…In fact, the reported daily level of 8-OHdG excretion in urine of healthy subjects is fairly low; 8-OHdG/Crn: 2.03 ± 1.21 and 1.86 ± 1.09 μmole/mole (spot urine and 24-h urine, respectively: n = 67) (Figure 2A) (17); urinary 8-OHdG amount was also reported circa (ca.) 2.2 (1.7-2.8) and 6.05 (3.12-15.38) nmole/24 h, for control subjects (n = 85) and patients (n = 222), respectively (18). This means that dG scavenges 2-16 nmoles of •OH daily.…”

“…Since we know that urinary (CTL + MG) and DMC are roughly in a one to one ratio (1,5), we estimated the amount of DMC from the corresponding measured amount of CTL plus MG: the total sum might be nearly equal to 2 × (CTL + MG). Furthermore, we wanted to show in this mini-review that the wellknown urinary level of 8-hydroxydeoxyguanosine (8-OHdG) ( Figure 1B) (17,18). However, we wanted to cite papers reporting that 8-OHdG could be a useful marker of •OH inside the nucleus and mitochondria (19).…”

Thiobarbituric acid reactive substances (TBARS) is a state biomarker of oxidative stress in bipolar patients in a manic phase

“…SOD, GPx and CAT are primary antioxidant enzymes that act against oxidative stress and prevent the oxidation of DNA, protein and lipid (Sabens Liedhegner et al, 2012;Roszkowski, 2014). SOD is the first line of defense in scavenging the superoxide anion radical (O 2 À ), which has been reported as both decreased and increased in manic patients (Andreazza et al, 2007a;Gergerlioglu et al, 2007;Machado-Vieira et al, 2007;Kunz et al, 2008).…”

Oxidative damage in DNA bases revealed by UV resonant Raman spectroscopy

“…superoxide, hydrogen peroxide, and hydroxyl radicals) play an important role. 5 Cells have many intracellular antioxidant defence mechanisms, but some conditions may cause failure in the neutralization events. However, when their production exceeds antioxidant defences, ROS attack and damage cellular components like proteins, lipids and nucleic acids DNA.…”

“…3 ROS are produced in cells during normal metabolic processes involving oxygen and they have an important catalytic role. 5,6 Under physiological conditions, the main species responsible for the genomic damage is the hydroxyl radical (OH • ) which induces the generation of a number of DNA base derivatives. 3,4 The production of ROS may be significantly increased by exposure to different environmental toxins derived from industry, agriculture, tobacco smoke, or pollution accidents.…”