PHOTOTOXICITY OF SOME NOVEL PORPHYRIN HYBRIDS AGAINST THE HUMAN LEUKEMIC-CELL LINE TF-1

Photodynamic induced cytotoxicity by porphyrin-DNA cross linker/interc alator hybrid diads and triads has been studied on the human leukemic cell line TF-1. Cells were incubated for 1 to 4 h with these new photo sensitizers and irradiated with white light. Cell survival was assesse d by the propidium iodide staining, using flow cytometry analysis. A c omparison of the dark and light cell survival factor values suggests t hat irradiation has a significant effect on the toxicity at low concen trations for the porphyrin-chlorambucil diad and to a lesser extent at high concentrations for the porphyrin-acridone diad, the porphyrin-ac ridine diad and the porphyrin-cholic acid-chlorambucil triad. While th e intrinsic antileukemic (via DNA cross-linking) activity of the chlor ambucil moiety and the structural details may be responsible for the p hotoenhancement of the toxicity, the presence of acridine or acridone which are avid intercalators of DNA, is responsible for a similar effe ct seen for diads. (C) 1997 Elsevier Science S.A.