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 nucleoside 8-oxo-7,8-dehydro-2'-deoxyguanosine (8-oxo-dGuo) in urine of adriamycin-treated cancer patients. Adriamycin has been shown to generate oxygen 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 semipreparative HPLC. Here we report the results of a study involving 20 cancer patients treated with flash doses of ADR. We found that urine HMUra is significantly increased (HMUra (nmol/24h): 80.8 8.44 vs. 98.7+/-6.87; p < 0.01) 24h after administration of the drug, while 8-oxo-dGuo did not show any significant variation. Urine HMUra seems to be a suitable short-term marker of DNA alterations by oxygen free radicals.
G.R.E.P.O., Faculté de Médecine-Pharmacie, La Tronche, France.
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Faure
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Mousseau
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Guimier
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D000080242:8-Hydroxy-2'-Deoxyguanosine; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D004247:DNA / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000652:urine*; D010084:Oxidation-Reduction; D010432:Pentoxyl / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D000903:Antibiotics, Antineoplastic; D017392:Thiobarbituric Acid Reactive Substances; C008055:5-hydroxymethyluracil; D010432:Pentoxyl; D004317:Doxorubicin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine