Further evidence that the radioprotective aminothiol, WR-1065, catalytically inactivates mammalian topoisomerase II.
Cancer Res
; 60(5): 1186-8, 2000 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-10728671
ABSTRACT
It has recently been proposed that the thiol form of the cytoprotective drug amifostine that is designated WR-1065 [2-((aminopropyl)amino)ethanethiol] exerts its cytoprotective effects in part via a catalytic inhibition of DNA topoisomerase II (topo II)alpha. This in turn leads to the subsequent accumulation of cells in G2 phase and a prolongation of the cell cycle. We have used a Chinese hamster V79 cell-based micronucleus assay to further evaluate this hypothesis. It is demonstrated that WR-1065 strongly inhibits the clastogenesis of the topo II poisons etoposide and clinafloxacin at clinically attained exposure levels while having no effect on clastogenesis induced by topo II-noninteractive chemicals. These findings are consistent with the hypothesis that WR-1065 is a catalytic inhibitor of topo II in mammalian cells. These studies also suggest that WR-1065 might be expected to reduce the toxicity and clastogenicity in clinical applications of etoposide or quinolone antibiotics in dose-limiting normal tissues.
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Base de dados:
MEDLINE
Assunto principal:
Protetores contra Radiação
/
Inibidores da Topoisomerase II
/
Mercaptoetilaminas
Idioma:
En
Ano de publicação:
2000
Tipo de documento:
Article