Alkylation of DNA by the new anticancer agent 3,6-diaziridinyl-2,5-bis(carboethoxyamino)-1,4-benzoquinone (AZQ).
The bifunctional cross-linking activity of 3,6-diaziridinyl-2,5-bis(carboethoxyamino)-1,4-benzoquinone (AZQ, NSC 182986) on isolated calf thymus DNA was studied, using ethidium bromide fluorescence assay. Between 1 and 350 microM AZQ produced a dose-dependent cross-linking effect in the presence of a 10-fold excess of sodium borohydride. No cross-linking was observed in the absence of the reducing agent. AZQ can also be activated by NADH and NADPH at pH 4. The AZQ cross-linking activity exhibited a strong pH dependency, highest at acidic pH, lower at alkaline pH and not seen under neutral conditions. It was also significantly inhibited under anaerobic conditions. At pH 5 the binding ratio was 1 molecule of AZQ per 191 bases at an AZQ dose of 300 microM. Our results suggest that reduced AZQ behaved like a bifunctional alkylating agent.
D000478:Alkylation; D000818:Animals; D000970:Antineoplastic Agents; D001388:Aziridines; D001389:Azirines; D016227:Benzoquinones; D001894:Borohydrides; D002417:Cattle; D003432:Cross-Linking Reagents; D004247:DNA; D006863:Hydrogen-Ion Concentration; D010084:Oxidation-Reduction; D010100:Oxygen; D013950:Thymus Gland / Q000032:analysis
D000970:Antineoplastic Agents; D001388:Aziridines; D001389:Azirines; D016227:Benzoquinones; D001894:Borohydrides; D003432:Cross-Linking Reagents; C025364:sodium borohydride; D004247:DNA; C029108:diaziquone; D010100:Oxygen