HYPERSENSITIVITY OF LYMPHOBLASTOID LINES DERIVED FROM ATAXIA-TELANGIECTASIA PATIENTS TO THE INDUCTION OF CHROMOSOMAL-ABERRATIONS BY ETOPOSIDE (VP-16)

被引:18
作者
CAPOROSSI, D
PORFIRIO, B
NICOLETTI, B
PALITTI, F
DEGRASSI, F
DESALVIA, R
TANZARELLA, C
机构
[1] UNIV FLORENCE,DEPT CLIN PHYSIOPATHOL,I-50121 FLORENCE,ITALY
[2] LA TUSCIA UNIV,DEPT AGROBIOL,VITERBO,ITALY
[3] CNR,CTR GENET EVOLUZIONIST,ROME,ITALY
[4] UNIV ROMA LA SAPIENZA,DEPT GENET & MOLEC BIOL,I-00185 ROME,ITALY
来源
MUTATION RESEARCH | 1993年 / 290卷 / 02期
关键词
ATAXIA TELANGIECTASIA; VP-16; CHROMOSOMAL ABERRATIONS;
D O I
10.1016/0027-5107(93)90167-E
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Mammalian DNA topoisomerase II represents the cellular target of many antitumor drugs, such as epipodophyllotoxin VP-16 (etoposide). The mechanism by which VP-16 exerts its cytotoxic and antineoplastic actions has not yet been firmly established, although the unique correlation between sensitivity to ionizing radiation and to topoisomerase II inhibitors suggest the involvement of DNA double-strand breaks. In the present study we analyzed the chromosomal sensitivity of lymphoblastoid cell lines derived from ataxia telangiectasia (AT) patients to low concentrations of the drug. Our results indicate that AT derived cells are hypersensitive to the clastogenic activity of VP-16 either when the drug is present for the whole duration of the cell cycle or specifically in the G2 phase, confirming that the induction of DNA double strand breaks, to which AT cells seem typically sensitive, could have an important role in the biological activity of VP-16.
引用
收藏
页码:265 / 272
页数:8
相关论文
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