GENOTOXIC ACTIVITY OF AZIDOTHYMIDINE (AZT) IN IN-VITRO SYSTEMS

被引:31
作者
CID, MG
LARRIPA, I
机构
[1] Departamento de Genética, Instituto de Investigaciones Hematológicas Mariano R. Castex, Academia Nacional de Medicina, 1425 Buenos Aires
来源
MUTATION RESEARCH | 1994年 / 321卷 / 1-2期
关键词
AZIDOTHYMIDINE (AZT); HUMAN LYMPHOCYTES; CHO CELL LINE; CHROMOSOME DAMAGE;
D O I
10.1016/0165-1218(94)90127-9
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The genotoxic activity of azidothymidine (AZT) was evaluated in vitro, measuring cytogenetic parameters in two cell systems. In human lymphocytes AZT induced a statistically significant increase in chromosome breakage at 100 mug/ml and in micronucleated cells at the highest dose assayed (500 mug/ml). Sister-chromatid exchanges (SCE) showed a two-fold increase over control values at 50 mug/ml. Lymphocyte cycle kinetics showed an important delay at 500 mug/ml. In Chinese hamster ovary (CHO) cells, AZT produced a significant increase in chromosome aberrations and SCE at 1000 and 500 mug/ml, respectively. At 2500 mug/ml the drug produced a delay in cell cycle progression. These results suggest that AZT is a DNA-damaging agent in both cell systems assayed. Moreover, human lymphocytes seem to be more sensitive to AZT than CHO cells.
引用
收藏
页码:113 / 118
页数:6
相关论文
共 23 条
[1]  
ABE S, 1982, PROGR TOPICS CYTOGEN, V2, P461
[2]  
AUERBACH AD, 1981, PEDIATRICS, V67, P128
[3]   SENSITIVITY OF 2 CHINESE-HAMSTER CELL-LINES TO SCE INDUCTION BY A VARIETY OF CHEMICAL MUTAGENS [J].
BAKER, RSU ;
MITCHELL, GA ;
MEHERHOMJI, KM ;
PODOBNA, E .
MUTATION RESEARCH, 1983, 118 (1-2) :103-116
[4]   CHROMOSOMAL-ABERRATIONS IN CULTURED HUMAN-LYMPHOCYTES TREATED WITH ALDICARB, A CARBAMATE PESTICIDE [J].
CID, MG ;
MATOS, E .
MUTATION RESEARCH, 1987, 191 (02) :99-103
[5]   PRODUCTION OF MICRONUCLEI FROM CHROMOSOME-ABERRATIONS IN IRRADIATED CULTURES OF HUMAN LYMPHOCYTES [J].
COUNTRYMAN, PI ;
HEDDLE, JA .
MUTATION RESEARCH, 1976, 41 (2-3) :321-331
[6]  
KOUZAN S, 1989, THERAPIE, V44, P393
[7]   ZIDOVUDINE - A REVIEW OF ITS PHARMACODYNAMIC AND PHARMACOKINETIC PROPERTIES, AND THERAPEUTIC EFFICACY [J].
LANGTRY, HD ;
CAMPOLIRICHARDS, DM .
DRUGS, 1989, 37 (04) :408-450
[8]   ZIDOVUDINE - 5 YEARS LATER [J].
MCLEOD, GX ;
HAMMER, SM .
ANNALS OF INTERNAL MEDICINE, 1992, 117 (06) :487-501
[9]  
MCNALLY A, 1983, CYTOBIOS, V38, P159
[10]   3'-AZIDO-3'-DEOXYTHYMIDINE (BW A509U) - AN ANTIVIRAL AGENT THAT INHIBITS THE INFECTIVITY AND CYTOPATHIC EFFECT OF HUMAN LYMPHOTROPIC-T VIRUS TYPE-III LYMPHADENOPATHY-ASSOCIATED VIRUS INVITRO [J].
MITSUYA, H ;
WEINHOLD, KJ ;
FURMAN, PA ;
STCLAIR, MH ;
LEHRMAN, SN ;
GALLO, RC ;
BOLOGNESI, D ;
BARRY, DW ;
BRODER, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (20) :7096-7100