title: Oxidative damage to guanine nucleosides following combination chemotherapy with 5-fluorouracil and oxaliplatin.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  These results indicate that FOLFOX induces ROS in patients and that ROS-generating mechanisms interact.
authors.affiliation: Laboratory of Clinical Pharmacology Q7642, Rigshospitalet, 20 Tagensvej, 2200 Copenhagen, Denmark. shoaibafzal@hotmail.com
authors.forename: Shoaib
authors.initials: S
authors.lastname: Afzal
authors.forename: Søren Astrup
authors.initials: SA
authors.lastname: Jensen
authors.forename: Jens Benn
authors.initials: JB
authors.lastname: Sørensen
authors.forename: Trine
authors.initials: T
authors.lastname: Henriksen
authors.forename: Allan
authors.initials: A
authors.lastname: Weimann
authors.forename: Henrik Enghusen
authors.initials: HE
authors.lastname: Poulsen
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000652:urine; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006151:Guanosine / Q000031:analogs & derivatives / Q000652:urine; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D011446:Prospective Studies; D053719:Tandem Mass Spectrometry; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D006151:Guanosine; C046215:8-hydroxyguanosine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D005472:Fluorouracil