Localization of cytochrome P4501A1 and covalent binding of a mutagenic heterocyclic amine in blood vessel endothelia of rodents

被引:19
作者
Annas, A [1 ]
Brittebo, EB [1 ]
机构
[1] Uppsala Univ, Dept Pharmaceut Biosci, Div Toxicol, SE-75124 Uppsala, Sweden
关键词
CYP1A1; endothelium; food mutagen; heart; immunohistochemistry; lymph node; muscle; uterus;
D O I
10.1016/S0300-483X(98)00087-0
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Immunohistochemistry was used to examine the cellular localization of cytochrome P4501A1 (CYP1A1) in various types of endothelial linings in muscle tissues of rats and mice treated with the Ah receptor agonist beta-naphthoflavone (BNF). In addition, light microscopic autoradiography was used to localize sites of metabolic activation of H-3-labeled Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole), a heterocyclic amine known to be metabolized by CYP1A1, in rodent tissue slices. The results showed a colocalization of CYP1A1 immunoreactivity and covalent binding of H-3-Trp-P-1 in endothelial linings of capillaries and veins of heart, skeletal muscle, and uterus in BNF-treated rodents, indicating the presence of catalytically active CYP1A1 at these sites. The immunohistochemical staining and covalent binding of H-3-Trp-P-1 in endothelia of arteries and arterioles was generally weak with the exception of uterine arterioles. In lymph nodes of BNF-treated rats, there was an intense CYP1A1 staining of high endothelial venules. The results suggest that endothelial linings of capillaries and veins in muscle tissues but also uterine arterioles and high endothelial venules in lymph nodes may be targets for CYP1A1-mediated metabolic products of endogenous and exogenous substances following exposure to CYP1A1 inducing agents. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:145 / 156
页数:12
相关论文
共 56 条
  • [1] IDENTIFICATION OF HEME OXYGENASE AND CYTOCHROME-P-450 IN THE RABBIT HEART
    ABRAHAM, NG
    PINTO, A
    LEVERE, RD
    MULLANE, K
    [J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1987, 19 (01) : 73 - 81
  • [2] PRESENCE OF CYTOCHROME-P-450-DEPENDENT MONOOXYGENASE IN INTIMAL CELLS OF THE HOG AORTA
    ABRAHAM, NG
    PINTO, A
    MULLANE, KM
    LEVERE, RD
    SPOKAS, E
    [J]. HYPERTENSION, 1985, 7 (06) : 899 - 904
  • [3] Endothelium-derived hyperpolarizing factor - Characterization as a cytochrome P450 1A-linked metabolite of arachidonic acid in perfused rat mesenteric prearteriolar bed
    Adeagbo, ASO
    [J]. AMERICAN JOURNAL OF HYPERTENSION, 1997, 10 (07) : 763 - 771
  • [4] ANDERSON LM, 1987, CANCER RES, V47, P6079
  • [5] Induction of ethoxyresorufin O-deethylase (EROD) and endothelial activation of the heterocyclic amine Trp-P-1 in bird embryo hearts
    Annas, A
    Brunström, B
    Brandt, I
    Brittebo, EB
    [J]. ARCHIVES OF TOXICOLOGY, 1998, 72 (07) : 402 - 410
  • [6] IMMUNOHISTOCHEMICAL DETECTION OF PULMONARY CYTOCHROME P450IA AND METABOLIC-ACTIVITIES ASSOCIATED WITH P450IA1 AND P450IA2 ISOZYMES IN LUNG-CANCER PATIENTS
    ANTTILA, S
    VAINIO, H
    HIETANEN, E
    CAMUS, AM
    MALAVEILLE, C
    BRUN, G
    HUSGAFVELPURSIAINEN, K
    HEIKKILA, L
    KARJALAINEN, A
    BARTSCH, H
    [J]. ENVIRONMENTAL HEALTH PERSPECTIVES, 1992, 98 : 179 - 182
  • [7] SMOKING AND PERIPHERAL TYPE OF CANCER ARE RELATED TO HIGH-LEVELS OF PULMONARY CYTOCHROME-P450IA IN LUNG-CANCER PATIENTS
    ANTTILA, S
    HIETANEN, E
    VAINIO, H
    CAMUS, AM
    GELBOIN, HV
    PARK, SS
    HEIKKILA, L
    KARJALAINEN, A
    BARTSCH, H
    [J]. INTERNATIONAL JOURNAL OF CANCER, 1991, 47 (05) : 681 - 685
  • [8] METABOLISM OF BENZO[A]PYRENE AND 7,12-DIMETHYLBENZ[A]ANTHRACENE IN CULTURED HUMAN-FETAL AORTIC SMOOTH-MUSCLE CELLS
    BOND, JA
    KOCAN, RM
    BENDITT, EP
    JUCHAU, MR
    [J]. LIFE SCIENCES, 1979, 25 (05) : 425 - 430
  • [9] BRITTEBO EB, 1994, CANCER RES, V54, P2887
  • [10] BRITTEBO EB, 1987, CANCER RES, V47, P1449