Photocytotoxicity of anthracyclines upon laser excitation in their long-wavelength absorption bands.
Newly synthesized daunomycin derivatives with red-shifted absorption compared to the parent molecule are shown to be able to photosensitize cells in vitro upon excitation with either argon or argon-pumped dye laser. Administering 86 J/cm2 total fluence (1 h irradiation) to Fisher rat thyroid cells during 2 h incubation with either daunomycin (excitation wavelength: 488 nm) or 5-iminodaunomycin (595 nm) produced cell killing at doses (about 2.7 X 10(-7) M for 50% cell survival) which were not toxic if administered in the dark. Greater photocytotoxicity (about 7 X 10(-8) M for 50% cell survival) was obtained with 4-demethoxydaunomycin as well as with its 6- and 11-amino derivatives (514 nm) while no cell killing as a result of photosensitization was observed for either Adriamycin or its 4'-iodo derivative. Our results suggest that the photosensitizing efficacy correlates with the absence of the methoxy group in the anthraquinone chromophore but is rather independent of the occurrence of triplet-mediated photoreactions. Finally, the fact that the imino- or amino-substituted 4-demethoxy compounds exhibit red-shifted absorption spectra compared to the parent molecule might be exploited for in vivo applications of the photoactivated cytotoxicity reported in this work.
Andreoni
A
A
Centro Endocrinologia ed Oncologia Sperimentale-C.N.R., University of Naples, Italy.
Colasanti
A
A
Malatesta
V
V
Roberti
G
G
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D003630:Daunorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D010778:Photochemotherapy; D051381:Rats; D011916:Rats, Inbred F344
D000903:Antibiotics, Antineoplastic; C053044:4'-deoxy-4'-iododoxorubicin; D004317:Doxorubicin; C018979:5-iminodaunorubicin; D003630:Daunorubicin