title: DNA topoisomerase II as the cellular target of a novel antitumor agent ICRF-193, a bisdioxopiperazine derivative, in Xenopus egg extract.
abstract: We have investigated the molecular target of an antitumor agent ICRF-193, a bisdioxopiperazine derivative, in in vitro chromosome condensation system of Xenopus egg extract (XEE), where DNA topoisomerase II was previously demonstrated to play a crucial role. Demembranated Xenopus sperm head chromatin is converted to metaphase chromosome-like structure in XEE in two steps, i.e., swelling of the chromatin followed by condensation of chromosome. When ICRF-193 was added to the reaction, swelling of the chromatin was not affected but chromosome condensation was completely blocked. This blockade was reversed by exogenous supplement of calf thymus topoisomerase II, which was in turn neutralized by anti-topoisomerase II monoclonal antibody. These results demonstrate that topoisomerase II is the molecular target of the drug ICRF-193.
authors.affiliation: Research Laboratory, Zenyaku Kogyo Co., Ltd., Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: R
authors.initials: R
authors.lastname: Ishida
authors.forename: K
authors.initials: K
authors.lastname: Ohsumi
authors.forename: T
authors.initials: T
authors.lastname: Narita
authors.forename: T
authors.initials: T
authors.lastname: Andoh
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002843:Chromatin / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D002875:Chromosomes / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D054659:Diketopiperazines; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008297:Male; D009865:Oocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D010879:Piperazines / Q000494:pharmacology*; D013077:Sperm Head; D059005:Topoisomerase II Inhibitors; D014982:Xenopus laevis
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D002843:Chromatin; D054659:Diketopiperazines; D004791:Enzyme Inhibitors; D010879:Piperazines; D059005:Topoisomerase II Inhibitors; C070899:4,4'-(1,2-dimethyl-1,2-ethanediyl)bis-2,6-piperazinedione