Spectral shape modifications of anthracyclines bound to cell nuclei: a microspectrofluorometric study.
Anthracyclines remain today the medications of choice against a wide spectrum of human cancers. Anthracyclines are fluorescent molecules and microfluorimetric methods are often used to determine their cellular distribution. The use of microspectrofluorometric techniques yields additional information because not only the fluorescence intensity but also the spectral modifications of the chromophore can be used to assess the intracellular drug concentration, its localisation and also eventually its metabolisation. It is well-documented that the shape of the fluorescence spectrum of anthracyclines changes markedly with the hydrophobicity of their environment. This change can be quantitatively measured by the ratio rho of the fluorescence emission intensities at 560 and 590 nm. We have observed that the shape of the fluorescent spectrum of adriamycin, daunorubicin and 4'-O-tetrahydropyranyladriamycin recorded from a small volume inside the cell nucleus was strongly dependent on the drug concentration and that the rho value decreases as the drug concentration increases. These data were compared with the rho variations when the drugs were either dissolved in different solvents or intercalated between the base pairs of DNA. We arrived at the conclusion that the shape variation of the drug spectra was not due to a change in their hydrophobicity environment but to an excitonic coupling of the electric dipolar transition moments of the pi --> pi* transition.
Laigle
A
A
Laboratoire de Physicohimie Biomolèculaire et Cellulaire (UA CNRS 2056), Université Paris Nord, Bobigny, France.
Fiallo
M M
MM
Garnier-Suillerot
A
A
D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D003630:Daunorubicin / Q000737:chemistry / Q000378:metabolism; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D013050:Spectrometry, Fluorescence
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D004247:DNA; C027260:pirarubicin; D003630:Daunorubicin