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01.02.2012 | Original Article

Oxidative damage to guanine nucleosides following combination chemotherapy with 5-fluorouracil and oxaliplatin

verfasst von: Shoaib Afzal, Søren Astrup Jensen, Jens Benn Sørensen, Trine Henriksen, Allan Weimann, Henrik Enghusen Poulsen

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 2/2012

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Abstract

Purpose

Recent in vitro and animal studies have suggested that the cytotoxicity of 5-fluorouracil and oxaliplatin is linked to increased formation of reactive oxygen species (ROS). This prospective study was undertaken to examine the generation of oxidative stress, in 106 colorectal cancer patients, by 5-fluorouracil and oxaliplatin combination (FOLFOX) therapy as measured by urinary excretion of 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydro-guanosine (8-oxoGuo).

Methods

The amounts of 8-oxoGuo and 8-oxodG were measured in 3 spot urine samples from 106 patients by using ultra performance liquid chromatography and tandem mass spectrometry. Furthermore, we collected information on other clinical and demographic variables hypothesized to be associated with oxidative stress. Repeated measures linear mixed models were used to model the relationship between urinary concentrations of 8-oxoGuo and 8-oxodG and the treatment effect and the other variables.

Results

The analysis showed that chemotherapy increased the excretion of 8-oxoGuo and 8-oxodG around 15% (P < 0.0001 and P = 0.02, respectively) though there was a significant interaction with CRP levels. Additionally, we found that sex, smoking status, age, and c-reactive protein were related to urinary excretion of 8-oxoGuo and 8-oxodG in colorectal cancer patients.

Conclusion

These results indicate that FOLFOX induces ROS in patients and that ROS-generating mechanisms interact.

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Titel: Oxidative damage to guanine nucleosides following combination chemotherapy with 5-fluorouracil and oxaliplatin
verfasst von: Shoaib Afzal
Søren Astrup Jensen
Jens Benn Sørensen
Trine Henriksen
Allan Weimann
Henrik Enghusen Poulsen
Publikationsdatum: 01.02.2012
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 2/2012
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-011-1700-2

Springer Medizin

Oxidative damage to guanine nucleosides following combination chemotherapy with 5-fluorouracil and oxaliplatin