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 malignancies, 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 being investigated for use in PDT. We have determined that the incubation of two human and two rodent tumor cell lines in culture with delta-ALA over a 24 h period results in an increase in the accumulation of fluorescent porphyrins in all of these cell lines. However, the two human cell lines produce fluorescent porphyrin at different rates from those seen in the rodent cell lines. The uptake of 14C-delta-ALA was concentration dependent, similar for all the cell lines studied and rapidly reached an intra/extracellular equilibrium after delta-ALA was added to the culture medium. The increase in intracellular fluorescent porphyrin was dependent on the level of delta-ALA in the medium and the incubation time and was directly related to the phototoxicity observed upon exposure of cultured monolayers to light. The data demonstrate that equivalent levels of phototoxicity can be attained by exposing cells 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 regimens that use delta-ALA.
Gibson
S L
SL
Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, NY, USA.
Havens
J J
JJ
Foster
T H
TH
Hilf
R
R
D000622:Aminolevulinic Acid / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002250:Carbon Radioisotopes; D006801:Humans; D007700:Kinetics; D008027:Light / Q000009:adverse effects*; D011166:Porphyrins / Q000096:biosynthesis* / Q000633:toxicity; D012377:Rodentia; D014407:Tumor Cells, Cultured
D002250:Carbon Radioisotopes; D011166:Porphyrins; D000622:Aminolevulinic Acid