Small field radiotherapy of head and neck cancer patients is responsible for oxidatively damaged DNA/oxidative stress on the level of a whole organism

Abstract

It is possible that oxidatively damaged DNA which arises as a result of radiotherapy may be involved in the therapeutic effect of the ionizing radiation and in the side effects. Therefore, for the first time, the broad spectrum of oxidatively damaged DNA biomarkers: urinary excretion of 8-oxodG (8-oxo-7,8-dihydro-2 0 -deoxyguanosine), as well as the level of oxidatively damaged DNA in leukocytes, was analyzed in head and neck cancer patients (n 5 27) undergoing fractionated radiotherapy using methodologies which involve HPLC (high-performance liquid chromatography) prepurification followed by gas chromatography with isotope dilution mass spectrometry detection and HPLC/EC. Of all the analyzed parameters in the majority of patients, only urinary excretion of the modified nucleoside significantly increased over the initial level in the samples collected 24 hr after the last fraction. However, for the distinct subpopulation of 10 patients, a significant increase in the level of 8-oxodG in cellular DNA and a simultaneous drop in urinary 8-oxoGua (the repair product of oxidative DNA damage) were detected after completion of the therapy. Because 8-oxoGua is a repair product of the DNA damage, there is a possibility that, at least in the case of some patients with the lowest activity of OGG1 (8-oxo-7,8-dihydroguanine glycosylase), the combination of lower OGG1 repair efficacy and irradiation was associated with increased background level of 8-oxoGua in cellular DNA. Apparently reduced DNA repair is unable to cope with the radiation-induced, and the extra amount of 8-oxoGua leading to an increase of potentially mutagenic/carcinogenic lesions.

Oxidative damage DNA: 8-oxoGua and 8-oxodG as molecular markers of cancer

“…A balance between producing ROS which induce oxidative DNA damages and removing these damages was observed in a cell (background level) [30]. According to some authors, the levels of these modifications do not depend on the type of cancer and histopathologic diagnosis [23,31–33]. …”

“…Several studies [19,20,23,31] have analyzed 8-oxoGua and 8-oxodG in urine in different types of cancer patients and control groups, reporting elevated level of 8-oxoGua in urine of cancer patients and in a control group of smoking subjects, and the level of 8-oxodG in DNA isolated from venous blood leucocytes was higher in the patient group.…”

“…In certain reports, a clear rise of 8-oxodG in urine excretion was observed after radio-chemotherapy or radiotherapy itself [21–23]. …”

Effect of surgical stress on nuclear and mitochondrial DNA from healthy sections of colon and rectum of patients with colorectal cancer

“…Since 8-OHdG is not metabolized, it is excreted in the urine (Cooke et al 2003;Crohns et al 2009). Indeed, many studies show the presence of 8-OHdG in urine or blood of patients with various cancers such as head and neck (Roszkowski et al 2008), breast (Haghdoost et al 2001), lung or colorectal cancer (Bialkowski et al 1996;Crohns et al 2009). This type of assay is the average 8-OHdG damage in the body and therefore may also depend on diet, the mechanisms of cell death and DNA repair (Wu et al 2004), and it does not allow us to distinguish the specific damage to the tissues.…”

Mass Spectrometry–Based Metabolomics Identifies Longitudinal Urinary Metabolite Profiles Predictive of Radiation-Induced Cancer

“…Decreased uric acid levels in the IR treated mice (Supplementary Figure S4G) were also observed. Uric acid is thought to be an antioxidant and this could contribute increased susceptibility to cancer induction/progression due to increased oxidative stress (25). Future studies will be focused on determining chemical structures of metabolites that either increase or decrease as a result of IR exposure.…”