Contrasting cytotoxic mechanisms of similar antitumour diaziridinylbenzoquinones.
The mechanisms of cytotoxicity of the antitumour diaziridinylbenzoquinones, AZQ and BZQ, have been investigated. HPLC analysis has been used to study the products as well as the rate of decomposition of acid-assisted ring-opening in aqueous medium as a function of pH. Microconcentrators with a molecular weight cutoff of 30 kDa were utilised to study the covalent binding of both compounds to calf thymus DNA. Radical production of both compounds in K562 cell incubations was followed using ESR and their uptake into K562 cells was monitored using radiolabelled compounds. The results show that these two diaziridinylbenzoquinones, although very similar in structure, have diverse mechanisms of cytotoxicity. The implications of these findings are discussed in the light of antitumor action.
Butler
J
J
Department of Biophysical Chemistry, Paterson Institute for Cancer Research, Christie Hospital and Holt Radium Institute, Manchester, U.K.
Dzielendziak
A
A
Lea
J S
JS
Ward
T H
TH
Hoey
B M
BM
D000477:Alkylating Agents; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001388:Aziridines / Q000032:analysis / Q000494:pharmacology*; D016227:Benzoquinones; D002470:Cell Survival / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000187:drug effects; D004355:Drug Stability; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D010084:Oxidation-Reduction
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D001388:Aziridines; D016227:Benzoquinones; D005609:Free Radicals; C045315:NSC 224070; D004247:DNA; C029108:diaziquone