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dc.contributor.authorRoszkowski, Krzysztof
dc.contributor.authorGackowski, Daniel
dc.contributor.authorRozalski, Rafal
dc.contributor.authorDziaman, Tomasz
dc.contributor.authorSiomek, Agnieszka
dc.contributor.authorGuz, Jolanta
dc.contributor.authorSzpila, Anna
dc.contributor.authorFoksinski, Marek
dc.contributor.authorOlinski, Ryszard
dc.date.accessioned2009-10-06T10:35:49Z
dc.date.available2009-10-06T10:35:49Z
dc.date.issued2008-10-15
dc.identifier.citationInt. J. Cancer 2008, 123 (8):1964-1967en
dc.identifier.issn1097-0215
dc.identifier.pmid18688851
dc.identifier.doi10.1002/ijc.23700
dc.identifier.urihttp://hdl.handle.net/10146/83613
dc.description.abstractIt 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'-deoxyguanosine), 8-oxoGua (8-oxo-7,8-dihydroguanine) as well as the level of oxidatively damaged DNA in leukocytes, was analyzed in head and neck cancer patients (n = 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.
dc.language.isoenen
dc.relation.urlhttp://www3.interscience.wiley.com/journal/121359650/abstract?CRETRY=1&SRETRY=0en
dc.subjectradiotherapyen
dc.subjectoxidatively damaged DNAen
dc.subject.meshChromatography, High Pressure Liquid
dc.subject.meshDNA Damage
dc.subject.meshDNA, Neoplasm
dc.subject.meshDeoxyguanosine
dc.subject.meshDose Fractionation
dc.subject.meshGas Chromatography-Mass Spectrometry
dc.subject.meshGuanine
dc.subject.meshHead and Neck Neoplasms
dc.subject.meshHumans
dc.subject.meshLeukocytes
dc.subject.meshOxidative Stress
dc.subject.meshRadiation Injuries
dc.subject.meshUric Acid
dc.titleSmall field radiotherapy of head and neck cancer patients is responsible for oxidatively damaged DNA/oxidative stress on the level of a whole organism.en
dc.typeArticleen
dc.identifier.journalInternational journal of cancer. Journal international du canceren
html.description.abstractIt 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'-deoxyguanosine), 8-oxoGua (8-oxo-7,8-dihydroguanine) as well as the level of oxidatively damaged DNA in leukocytes, was analyzed in head and neck cancer patients (n = 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.


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