title: A model for tumor cell killing by topoisomerase poisons.
abstract: Our model proposes that topoisomerase-targeting antitumor drugs form reversible drug-enzyme-DNA complexes that collide with the DNA and RNA synthesis machineries. On collision, the complexes lose their reversibility, and generate lethal double-strand DNA breaks. Further investigations of topoisomerase action will allow this model to be refined, and may ultimately lead to the development of more effective anticancer drugs.
authors.affiliation: Department of Biological Chemistry, Johns Hopkins School of Medicine, Baltimore, Maryland 21205.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: P
authors.initials: P
authors.lastname: D'Arpa
authors.forename: L F
authors.initials: LF
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects*; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
chemical_list: D000970:Antineoplastic Agents; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II