Quenching of DNA-ethidium fluorescence by amsacrine and other antitumor agents: a possible electron-transfer effect.
The antitumor agent amsacrine, 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA), when bound to double-stranded DNA, particularly poly(deoxyadenylicthymidylic acid), reduced the fluorescence of bound ethidium without physically displacing it from DNA. Fluorescence lifetime measurements showed that the reduction of fluorescence was not due to reduction of the lifetime of the excited state of ethidium. Rather, a proportion of the DNA-bound ethidium changed to a state where the fluorescence was highly quenched. Several other 9-anilinoacridine derivatives, and also 9-hydroxyellipticine, caused quenching of ethidium-DNA fluorescence, whereas 9-aminoacridine, proflavin, and ellipticine had no effect. Resonance energy transfer (Förster transfer) is not responsible for the effect since there is no spectral overlap between the absorption spectrum of any of the agents and the fluorescence emission spectrum of ethidium. It is suggested that quenching may occur as a result of reversible formation of electron-transfer complexes between the intercalating drug and the excited state of ethidium.
D000609:Aminoacridines; D000677:Amsacrine; D000818:Animals; D000970:Antineoplastic Agents; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D004247:DNA; D004269:DNA, Bacterial; D004279:DNA, Viral; D004996:Ethidium; D007700:Kinetics; D011067:Poly dA-dT; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D013950:Thymus Gland
D000609:Aminoacridines; D000970:Antineoplastic Agents; D004269:DNA, Bacterial; D004279:DNA, Viral; D000677:Amsacrine; D011067:Poly dA-dT; D004247:DNA; D004996:Ethidium