title: In vitro fluorescence, toxicity and phototoxicity induced by delta-aminolevulinic acid (ALA) or ALA-esters.
abstract: Synthesis of delta-aminolevulinic acid (ALA) derivatives is a promising way to improve the therapeutic properties of ALA, particularly cell uptake or homogeneity of protoporphyrin IX (PpIX) synthesis. The fluorescence emission kinetics and phototoxic properties of ALA-n-pentyl ester (E1) and R,S-ALA-2-(hydroxymethyl) tetrahydrofuranyl ester (E2) were compared with those of ALA and assessed on C6 glioma cells. ALA (100 micrograms/mL), E1 and E2 (10 micrograms/mL) induced similar PpIX-fluorescence kinetics (maximum between 5 and 7 h incubation), fluorescence being limited to the cytoplasm. The 50% lethal dose occurred after 6 h with 45, 4 and 8 micrograms/mL of ALA, E1 and E2, respectively. ALA, E1 and E2 induced no dark toxicity when drugs were removed after 5 min of incubation. However, light (25 J/cm2) applied 6 h after 5 min incubation with 168 micrograms/mL of each compound induced 85% survival with ALA, 27% with E1 and 41% with E2. Increasing the incubation time with ALA, E1 and E2 before washing increased the phototoxicity, but E1 and E2 remained more efficient than ALA, regardless of incubation time. ALA-esters were more efficient than ALA in inducing phototoxicity after short incubation times, probably through an increase of the amount of PpIX synthesized by C6 cells.
authors.affiliation: Département Laser, Hôpital Laënnec, Nantes, France.
authors.forename: S
authors.initials: S
authors.lastname: Eléouet
authors.forename: N
authors.initials: N
authors.lastname: Rousset
authors.forename: J
authors.initials: J
authors.lastname: Carré
authors.forename: L
authors.initials: L
authors.lastname: Bourré
authors.forename: V
authors.initials: V
authors.lastname: Vonarx
authors.forename: Y
authors.initials: Y
authors.lastname: Lajat
authors.forename: G M
authors.initials: GM
authors.lastname: Beijersbergen van Henegouwen
authors.forename: T
authors.initials: T
authors.lastname: Patrice
mesh_terms: D000622:Aminolevulinic Acid / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D004952:Esters; D005453:Fluorescence; D006801:Humans; D017319:Photosensitizing Agents / Q000633:toxicity*; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D004952:Esters; D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid