Severe oxidatively damaged DNA after cisplatin treatment of cancer patients.
There is growing evidence suggesting that cytotoxic activity of cisplatin is closely associated with increased generation of reactive oxygen species (ROS). Therefore, this study was undertaken to examine oxidative DNA damage, which arises as a result of chemotherapy with cisplatin. Using HPLC prepurification/isotope dilution GC/MS methodology, we examined the amount of 8-oxoGua and 8-oxodG excreted into urine in cancer patients (n = 66) who received chemotherapy with cisplatin. One day after the infusion of the drug, significant increase in the amount of 8-oxoGua and 8-oxodG in urine of the patients was observed, when compared to the initial value (78%, p < 0.0001 and 22%, p = 0.0051). In the "nadir days" (when the most distinct cell death based on hematological cell counts can be observed), the level of modified base and nucleoside decreased in comparison with the aforementioned time point. These results, for the first time, indicate that oxidatively damaged DNA may be, at least in part, responsible for cisplatin induced cytotoxicity. Our results also demonstrate that cell death does not contribute to urinary 8-oxoGua and 8-oxodG in humans.
Siomek
Agnieszka
A
Department of Clinical Biochemistry, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland.
Tujakowski
Jerzy
J
Gackowski
Daniel
D
Rozalski
Rafal
R
Foksinski
Marek
M
Dziaman
Tomasz
T
Roszkowski
Krzysztof
K
Olinski
Ryszard
R
D000970:Antineoplastic Agents / Q000627:therapeutic use; D002945:Cisplatin / Q000009:adverse effects*; D004249:DNA Damage / Q000187:drug effects*; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000652:urine; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D017382:Reactive Oxygen Species
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; C024829:8-hydroxyguanine; D006147:Guanine; D002945:Cisplatin