URINE 8-OXO-7,8-DIHYDRO-2'-DEOXYGUANOSINE VS. 5-(HYDROXYMETHYL) URACIL AS DNA OXIDATION MARKER IN ADRIAMYCIN-TREATED PATIENTS

We measured the base 5-(hydroxymethyl) uracil (HMUra) and the nucleosi de 8-oxo-7,8-dehydro-2'-deoxyguanosine (8-oxo-dGuo) in urine of adriam ycin-treated cancer patients. Adriamycin has been shown to generate ox ygen free radicals by various mechanisms. HMUra and 8-oxo-dGuo are two known lesions of DNA, produced by oxygen free reaction on thymine and 2'-deoxyguanosine, respectively. HMUra was measured by GC-MS/isotopic dilution and 8-oxo-dGuo by HPLC/EC, both after prepurification by sem ipreparative HPLC. Here we report the results of a study involving 20 cancer patients treated with flash doses of ADR. We found that urine H MUra is significantly increased (HMUra (nmol/24 h): 80.8 +/- 8.44 vs. 98.7 +/- 6.87; p < 0.01) 24 h after administration of the drug, while 8-oxo-dGuo did not show any significant variation. Urine HMUra seems t o be a suitable short-term marker of DNA alterations by oxygen free ra dicals.