METABOLISM OF DEBRISOQUINE AND SUSCEPTIBILITY TO BREAST-CANCER

被引:11
作者
HUOBER, J
BERTRAM, B
PETRU, E
KAUFMANN, M
SCHMAHL, D
机构
[1] GERMAN CANC RES CTR,INST TOXICOL & CHEMOTHERAPY,NEUENHEIMER FELD 280,W-6900 HEIDELBERG 1,GERMANY
[2] GRAZ UNIV,DEPT OBSTET & GYNECOL,A-8010 GRAZ,AUSTRIA
[3] UNIV HEIDELBERG,DEPT OBSTET & GYNECOL,W-6900 HEIDELBERG,GERMANY
关键词
BREAST CANCER; DEBRISOQUINE; GENETIC PHARMACOLOGY; METABOLISM;
D O I
10.1007/BF01975442
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
There may exist an association between the genetically determined oxidation status of the antihypertensive agent debrisoquine (DEB) and the propensity to develop tumours. The metabolism of DEB is extensive in 90% of healthy subjects (metabolic ratio = MR = 0-12.6; MR = % DEB excreted divided by %4-hydroxy-DEB excreted) and poor in 10% (MR > 12.6). In patients with cancer of the lung, urinary bladder, and gastrointestinum, the percentage of high metabolizers is increased to > 98%. The poor metabolizer mode is almost devoid of cancer patients. It was investigated whether breast cancer patients show a similar association with respect to the oxidative status of DEB. 108 breast cancer patients and 123 women with benign gynecologic disorders received 1 tablet of 10 mg DEB orally in the evening. Urine was collected for the subsequent 8 hrs and analysed for its content of DEB and its main urinary metabolite 4-OH-DEB by means of HPLC. No decreased amount of poor metabolizers was seen in the cancer group.
引用
收藏
页码:43 / 48
页数:6
相关论文
共 39 条
[11]  
EICHELBAUM M, 1988, GENETIC POLYMORPHISM, P243
[12]   A FAMILY AND POPULATION STUDY OF THE GENETIC-POLYMORPHISM OF DEBRISOQUINE OXIDATION IN A WHITE BRITISH-POPULATION [J].
EVANS, DAP ;
MAHGOUB, A ;
SLOAN, TP ;
IDLE, JR ;
SMITH, RL .
JOURNAL OF MEDICAL GENETICS, 1980, 17 (02) :102-105
[13]   CHARACTERIZATION OF THE COMMON GENETIC-DEFECT IN HUMANS DEFICIENT IN DEBRISOQUINE METABOLISM [J].
GONZALEZ, FJ ;
SKODA, RC ;
KIMURA, S ;
UMENO, M ;
ZANGER, UM ;
NEBERT, DW ;
GELBOIN, HV ;
HARDWICK, JP ;
MEYER, UA .
NATURE, 1988, 331 (6155) :442-446
[14]   P450-GENES - EVOLUTION, REGULATION, AND RELATIONSHIP TO HUMAN CANCER AND PHARMACOGENETICS [J].
GONZALEZ, FJ ;
JAISWAL, AK ;
NEBERT, DW .
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY, 1986, 51 :879-890
[15]  
GUENGERICH FP, 1988, CANCER RES, V48, P2946
[16]   ENZYMATIC ACTIVATION OF CHEMICALS TO TOXIC METABOLITES [J].
GUENGERICH, FP ;
LIEBLER, DC .
CRC CRITICAL REVIEWS IN TOXICOLOGY, 1985, 14 (03) :259-307
[17]   POLYMORPHISM OF HUMAN CYTOCHROME-P-450 [J].
GUENGERICH, FP ;
UMBENHAUER, DR ;
CHURCHILL, PF ;
BEAUNE, PH ;
BOCKER, R ;
KNODELL, RG ;
MARTIN, MV ;
LLOYD, RS .
XENOBIOTICA, 1987, 17 (03) :311-316
[18]   DETERMINATION OF DEBRISOQUINE AND ITS 4-HYDROXY METABOLITE IN URINE BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY [J].
HARRISON, PM ;
TONKIN, AM ;
DIXON, ST ;
MCLEAN, AJ .
JOURNAL OF CHROMATOGRAPHY, 1986, 374 (01) :204-208
[19]   POLYMORPHISMS OF OXIDATION AT CARBON CENTERS OF DRUGS AND THEIR CLINICAL SIGNIFICANCE [J].
IDLE, JR ;
SMITH, RL .
DRUG METABOLISM REVIEWS, 1979, 9 (02) :301-317
[20]  
KAISARY A, 1987, CANCER RES, V47, P5488