THE CYTOSTATIC ACTIVITY OF 5-(1-AZIDOVINYL)-2'-DEOXYURIDINE (AZVDU) AGAINST HERPES-SIMPLEX VIRUS THYMIDINE KINASE GENE-TRANSFECTED FM3A CELLS IS DUE TO INHIBITION OF THYMIDYLATE SYNTHASE AND ENHANCED BY UV-LIGHT (LAMBDA=254 NM) EXPOSURE

被引：12

作者：

BALZARINI, J ^{[1
]}

ANDREI, G ^{[1
]}

KUMAR, R ^{[1
]}

KNAUS, EE ^{[1
]}

WIEBE, LI ^{[1
]}

DECLERCQ, E ^{[1
]}

机构：

[1] UNIV ALBERTA,FAC PHARM & PHARMACEUT SCI,EDMONTON,AB T6G 2N8,CANADA

来源：

FEBS LETTERS | 1995年 / 373卷 / 01期

基金：

英国医学研究理事会;

关键词：

AZIDOVINYLDEOXYURIDINE; HERPES SIMPLEX VIRUS; THYMIDINE KINASE; GENE THERAPY; THYMIDYLATE SYNTHASE;

D O I：

10.1016/0014-5793(95)00994-K

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：

5-(1-Azidovinyl)-2'-deoxyuridine (AzVDU) and a series of 5-[1-azido-2-halogenoethyl]-derivatives of beta-D-arabinofuranosyluracil (AU) proved markedly inhibitory to the replication of herpes simplex virus type 1 (HSV-1) and varicella tester virus (VZV), but not thymidine kinase (TK)-deficient HSV-1 and VZV strains, None of the compounds were cytostatic, However, AzVDU, but not the 5-[1-azido-2-halogenoethyl]-AU derivatives became highly cytostatic against HSV-1 and HSV-2 TK gene-transfected FM3A tumor cells. The molecular target for the cytostatic effect of AzVDU proved to be thymidylate synthase, Short exposure of AzVDU-treated FM3A TK-/HSV-1 TK+ cells to irradiation at lambda = 254 nm enhanced the cytostatic activity of AzVDU by 5-fold.

引用

页码：41 / 44

页数：4

共 19 条

[1]

AYUSAWA D, 1985, JPN J CANCER RES, V76, P984

[2]

BALZARINI J, 1989, METHOD FIND EXP CLIN, V11, P379

[3]

BALZARINI J, 1987, MOL PHARMACOL, V32, P410

[4] STRATEGIES FOR THE MEASUREMENT OF THE INHIBITORY EFFECTS OF THYMIDINE ANALOGS ON THE ACTIVITY OF THYMIDYLATE SYNTHASE IN INTACT MURINE LEUKEMIA L1210-CELLS [J].

BALZARINI, J ;

DECLERCQ, E .

BIOCHIMICA ET BIOPHYSICA ACTA, 1984, 785 (1-2) :36-45

[5] MURINE MAMMARY FM3A CARCINOMA-CELLS TRANSFORMED WITH THE HERPES-SIMPLEX VIRUS TYPE-1 THYMIDINE KINASE GENE ARE HIGHLY SENSITIVE TO THE GROWTH-INHIBITORY PROPERTIES OF (E)-5-(2-BROMOVINYL)-2'-DEOXYURIDINE AND RELATED-COMPOUNDS [J].

BALZARINI, J ;

DECLERCQ, E ;

AYUSAWA, D ;

SENO, T .

FEBS LETTERS, 1985, 185 (01) :95-100

[6]

BALZARINI J, 1985, MOL PHARMACOL, V28, P581

[7]

BALZARINI J, 1995, GENE THER, V2, P317

[8]

BALZARINI J, 1994, MOL PHARMACOL, V45, P1253

[9]

BALZARINI J, 1994, INT ANTIVIRAL NEWS, V2, P82

[10] DEVELOPMENT OF ANTITUMOR IMMUNITY FOLLOWING THYMIDINE KINASE-MEDIATED KILLING OF EXPERIMENTAL BRAIN-TUMORS [J].

BARBA, D ;

HARDIN, J ;

SADELAIN, M ;

GAGE, FH .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (10) :4348-4352

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