Urine 8-oxo-7,8-dihydro-2′-deoxyguanosine vs. 5-(hydroxymethyl) uracil as DNA oxidation marker in adriamycin-treated patients

被引:37
作者
Faure, H
Mousseau, M
Cadet, J
Guimier, C
Tripier, M
Hida, H
Favier, A
机构
[1] CHU Grenoble, Lab Biochim C, Serv Oncol, F-38043 Grenoble 09, France
[2] Fac Med & Pharm, GREPO, F-38700 La Tronche, France
[3] CEA, SCIB, Dept Rech Fondamentale Mat Condensee, F-38054 Grenoble 9, France
关键词
DNA damage; 5-(hydroxymethyl) uracil; 8-oxo-7,8-dihydro-2 '-deoxyguanosine; adriamycin; human cancer;
D O I
10.3109/10715769809070806
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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/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 to be a suitable short-term marker of DNA alterations by oxygen free radicals.
引用
收藏
页码:377 / 382
页数:6
相关论文
共 24 条
[1]  
AMES BN, 1986, GENETIC TOXICOLOGY A, P11
[2]   SERUM CREATININE DETERMINATION WITHOUT PROTEIN PRECIPITATION [J].
BARTELS, H ;
BOHMER, M ;
HEIERLI, C .
CLINICA CHIMICA ACTA, 1972, 37 (NMAR) :193-&
[3]  
BERGTOLD DS, 1990, ADV EXP MED BIOL, V264, P311
[4]  
BERGTOLD DS, 1988, OXYGEN RADICALS BIOL, P483
[5]   SYNTHESIS OF 5-SUBSTITUTED PYRIMIDINES VIA FORMALDEHYDE ADDITION [J].
CLINE, RE ;
FINK, RM ;
FINK, K .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1959, 81 (10) :2521-2527
[6]   SENSITIZED PHOTOOXIDATION OF THYMIDINE BY 2-METHYL-1-1,4-NAPHTHOQUINONE - CHARACTERIZATION OF THE STABLE PHOTOPRODUCTS [J].
DECARROZ, C ;
WAGNER, JR ;
VANLIER, JE ;
KRISHNA, CM ;
RIESZ, P ;
CADET, J .
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 1986, 50 (03) :491-505
[7]   OXIDATIVE DAMAGE TO DNA IN MAMMALIAN CHROMATIN [J].
DIZDAROGLU, M .
MUTATION RESEARCH, 1992, 275 (3-6) :331-342
[8]   TOXICITY, SINGLE-STRAND BREAKS, AND 5-HYDROXYMETHYL-2'-DEOXYURIDINE FORMATION IN HUMAN BREAST EPITHELIAL-CELLS TREATED WITH HYDROGEN-PEROXIDE [J].
DJURIC, Z ;
EVERETT, CK ;
LUONGO, DA .
FREE RADICAL BIOLOGY AND MEDICINE, 1993, 14 (05) :541-547
[9]   GENOTOXICITY OF SINGLET OXYGEN [J].
EPE, B .
CHEMICO-BIOLOGICAL INTERACTIONS, 1991, 80 (03) :239-260
[10]   GAS-CHROMATOGRAPHIC MASS-SPECTROMETRIC DETERMINATION OF 5-HYDROXYMETHYLURACIL IN HUMAN URINE BY STABLE-ISOTOPE DILUTION [J].
FAURE, H ;
INCARDONA, MF ;
BOUJET, C ;
CADET, J ;
DUCROS, V ;
FAVIER, A .
JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS, 1993, 616 (01) :1-7