Small field radiotherapy of head and neck cancer patients is responsible for oxidatively damaged DNA/oxidative stress on the level of a whole organism.
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'-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.
Roszkowski
Krzysztof
K
Department of Radiotherapy, Center of Oncology, Romanowskiej 2, Bydgoszcz, Poland.
Gackowski
Daniel
D
Rozalski
Rafal
R
Dziaman
Tomasz
T
Siomek
Agnieszka
A
Guz
Jolanta
J
Szpila
Anna
A
Foksinski
Marek
M
Olinski
Ryszard
R
D000080242:8-Hydroxy-2'-Deoxyguanosine; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000378:metabolism / Q000528:radiation effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D019583:Dose Fractionation, Radiation; D008401:Gas Chromatography-Mass Spectrometry; D006147:Guanine / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000532:radiotherapy* / Q000652:urine; D006801:Humans; D007962:Leukocytes / Q000378:metabolism / Q000528:radiation effects; D018384:Oxidative Stress / Q000235:genetics; D011832:Radiation Injuries / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000652:urine; D014527:Uric Acid / Q000097:blood / Q000652:urine
D004273:DNA, Neoplasm; D014527:Uric Acid; C024829:8-hydroxyguanine; D006147:Guanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine