Recently, considerable interest has been given to
photodynamic therapy of
cancer using delta-aminolaevulinic
acid to induce
protoporphyrin IX as the cell
photosensitizer. One advantage of this modality is that
protoporphyrin IX is cleared from tissue within 24 h after delta-aminolaevulinic
acid administration. This could allow for multiple treatment regimens because of little concern regarding the accumulation of the
photosensitizer in normal tissues. However, the
haem biosynthetic pathway would have to be fully functional after the first course of
therapy to allow for subsequent treatments.
Photosensitization of cultured R3230AC rat mammary
adenocarcinoma cells with delta-aminolaevulinic
acid-induced
protoporphyrin IX resulted in the inhibition of
porphobilinogen deaminase, an
enzyme in the
haem biosynthetic pathway, and a concomitant decrease in
protoporphyrin IX levels. Cultured R3230AC cells exposed to 0.5 mM delta-aminolaevulinic
acid for 27 h accumulated 6.07 x 10(-16) mol of
protoporphyrin IX per cell and had a
porphobilinogen deaminase activity of 0.046 fmol uroporphyrin per 30 min per cell. Cells cultured under the same incubation conditions but exposed to 30 mJ cm(-2) irradiation after a 3-h incubation with delta-aminolaevulinic
acid showed a significant reduction in
protoporphyrin IX, 2.28 x 10(-16) mol per cell, and an 80% reduction in
porphobilinogen deaminase activity to 0.0088 fmol uroporphyrin per 30 min per cell. Similar effects were evident in irradiated cells incubated with delta-aminolaevulinic
acid immediately after, or following a 24 h interval, post-irradiation. There was little gain in efficacy from a second treatment regimen applied within 24 h of the initial treatment, probably a result of initial metabolic damage leading to reduced levels of
protoporphyrin IX. These findings suggest that a correlation may exist between the delta-aminolaevulinic
acid induction of
porphobilinogen deaminase activity and the increase in intracellular
protoporphyrin IX accumulation.