TIME-DEPENDENT INTRACELLULAR ACCUMULATION OF DELTA-AMINOLEVULINIC-ACID, INDUCTION OF PORPHYRIN SYNTHESIS AND SUBSEQUENT PHOTOTOXICITY

Photodynamic therapy (PDT), a novel treatment for a variety of human m alignancies, usually consists of visible light irradiation of lesions following the systemic administration of a photosensitizer, Induction of the endogenous photosensitizer protoporphyrin IX by the systemic or topical administration of delta-aminolevulinic acid (delta-ALA) is be ing investigated for use in PDT, We have determined that the incubatio n of two human and two rodent tumor cell lines in culture with delta-A LA over a 24 h period results in an increase in the accumulation of fl uorescent porphyrins in all of these cell lines. However, the two huma n cell lines produce fluorescent porphyrin at different rates from tho se seen in the rodent cell lines. The uptake of C-14-delta-ALA was con centration dependent, similar for all the cell lines studied and rapid ly reached an intra/extracellular equilibrium after delta-ALA was adde d to the culture medium, The increase in intracellular fluorescent por phyrin was dependent on the level of delta-ALA in the medium and the i ncubation time and was directly related to the phototoxicity observed upon exposure of cultured monolayers to light, The data demonstrate th at equivalent levels of phototoxicity can be attained by exposing cell s to 0.04 mM delta-ALA for 24 h or to 0.5 mM delta-ALA for 2 h, These findings may have implications for optimization of PDT treatment regim ens that use delta-ALA.