Antitumor drugs as photochemotherapeutic agents

Alessandra Andreoni; Alberto Colasanti; Annamaria Kisslinger; Vincenzo Malatesta; Michele Mastrocinque; Giuseppe Roberti

doi:10.1117/12.48198

1 November 1991 Antitumor drugs as photochemotherapeutic agents

Alessandra Andreoni, Alberto Colasanti, Annamaria Kisslinger, Vincenzo Malatesta, Michele Mastrocinque, Giuseppe Roberti

Author Affiliations +

Proceedings Volume 1525, Future Trends in Biomedical Applications of Lasers; (1991) https://doi.org/10.1117/12.48198
Event: MedTech '91, 1991, Berlin, Germany

Abstract

Irradiation with 86 J/cm2 of cultures of Fisher-rate thyroid cells (FRTL5) in the presence of daunomycin derivatives at wavelengths between 488 and 595 nm i.e., in the visible- absorption bands of these drugs, is shown to enhance their cytotoxicity. Daunomycin, its 4- demethoxy derivative, 5-iminodaunomycin, and two amino-substituted 4-demethoxy derivatives of daunomycin are tested. While a 2-h exposure to the drugs in the dark produces 50 short-term cell mortality at dosages (LD50) in the range 23 to 138 (mu) g/ml, irradiation administered during the cell exposure to the drugs is found to lower the LD50 values down to the range 45 to 289 ng/ml. Furthermore, while the LD50 values for all drugs in the absence of photoactivation are similar, if light is administered those for the 4- demethoxy compounds are lowered by 3 orders of magnitude and those for the other derivatives by 2 orders of magnitude. Microfluorimetric investigations reveal that photoactivation causes fading of the drug fluorescence in the perinuclear cytoplasm. The effect is more pronounced for drugs with higher photosensitizing properties. The nonfluorescent photoproducts which are formed in the cells during photoactivation exhibit a cytotoxic activity that is, at long term, lower than that of the original drug. The authors cannot yet assess which excited-state property of anthracyclines plays the key role in the photosensitized reaction(s) responsible for both short-term cell kill and long-term toxic effects. The show, however, that such property is strongly affected by the removal of the methoxy group from the C4 position.

Citation Download Citation

Alessandra Andreoni, Alberto Colasanti, Annamaria Kisslinger, Vincenzo Malatesta, Michele Mastrocinque, and Giuseppe Roberti "Antitumor drugs as photochemotherapeutic agents", Proc. SPIE 1525, Future Trends in Biomedical Applications of Lasers, (1 November 1991); https://doi.org/10.1117/12.48198

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