Identification of the major tamoxifen-DNA adducts in rat liver by mass spectroscopy

被引:46
作者
Rajaniemi, H [1 ]
Rasanen, I
Koivisto, P
Peltonen, K
Hemminki, K
机构
[1] Karolinska Inst, Novum, Dept Biosci, S-14157 Huddinge, Sweden
[2] Univ Helsinki, Dept Forens Med, FIN-00014 Helsinki, Finland
[3] Inst Occupat Hlth, FIN-00250 Helsinki, Finland
关键词
D O I
10.1093/carcin/20.2.305
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We present here the first mass spectroscopic (MS) identification of the main tamoxifen-induced DNA adducts in rat liver. The two main adducts were isolated by highperformance liquid chromatography (HPLC) and identified by MS, MS-MS and ultraviolet spectroscopy. Adduct 1 was the N-desmethyltamoxifen-deoxyguanosine adduct in which the a-position of the metabolite N-desmethyltamoxifen is linked covalently to the amino group of deoxyguanosine, Adduct 2 was confirmed to be the trans isomer of a(N-2-deoxyguanosinyl)tamoxifen, as previously suggested by co-chromatography.
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页码:305 / 309
页数:5
相关论文
共 25 条
  • [1] [Anonymous], IARC MONOGRAPHS EVAL
  • [2] DANIEL P, 1981, EUR J CANCER CLIN ON, V17, P1183
  • [3] Identification of tamoxifen-DNA adducts formed by alpha-sulfate tamoxifen and alpha-acetoxytamoxifen
    Dasaradhi, L
    Shibutani, S
    [J]. CHEMICAL RESEARCH IN TOXICOLOGY, 1997, 10 (02) : 189 - 196
  • [4] The metabolic activation of tamoxifen and α-hydroxytamoxifen to DNA-binding species in rat hepatocytes proceeds via sulphation
    Davis, W
    Venitt, S
    Phillips, DH
    [J]. CARCINOGENESIS, 1998, 19 (05) : 861 - 866
  • [5] STUDIES OF TAMOXIFEN AS A PROMOTER OF HEPATOCARCINOGENESIS IN FEMALE FISCHER F344 RATS
    DRAGAN, YP
    FAHEY, S
    STREET, K
    VAUGHAN, J
    JORDAN, VC
    PITOT, HC
    [J]. BREAST CANCER RESEARCH AND TREATMENT, 1994, 31 (01) : 11 - 25
  • [6] HAN XL, 1992, CANCER RES, V52, P1360
  • [7] Tamoxifen-induced DNA adducts in leucocytes of breast cancer patients
    Hemminki, K
    Rajaniemi, H
    Koskinen, M
    Hansson, J
    [J]. CARCINOGENESIS, 1997, 18 (01) : 9 - 13
  • [8] Hemminki K, 1996, CANCER RES, V56, P4374
  • [9] THE DEUTERIUM-ISOTOPE EFFECT FOR THE ALPHA-HYDROXYLATION OF TAMOXIFEN BY RAT-LIVER MICROSOMES ACCOUNTS FOR THE REDUCED GENOTOXICITY OF [D-5-ETHYL]TAMOXIFEN
    JARMAN, M
    POON, GK
    ROWLANDS, MG
    GRIMSHAW, RM
    HORTON, MN
    POTTER, GA
    MCCAGUE, R
    [J]. CARCINOGENESIS, 1995, 16 (04) : 683 - 688
  • [10] Conformational studies and electronic structures of tamoxifen and toremifene and their allylic carbocations proposed as reactive intermediates leading to DNA adduct formation
    Kuramochi, H
    [J]. JOURNAL OF MEDICINAL CHEMISTRY, 1996, 39 (15) : 2877 - 2886