THE INFLUENCE OF HYPOXIA AND PH ON AMINOLEVULINIC ACID-INDUCED PHOTODYNAMIC THERAPY IN BLADDER-CANCER CELLS IN-VITRO

Photodynamic therapy (PDT) is a cancer treatment based on the interact ion of light and a photosensitizing chemical. The photosensitizer prot oporphyrin IX (PpIX) is generated via the haem biosynthetic pathway af ter administration of aminolaevulinic acid (ALA), The cellular microen vironment of tumours is hypoxic and acidotic relative to normal tissue , which may influence PpIX generation and compromise PDT efficacy. Thi s study used bladder cancer cells, incubated with ALA at various oxyge n tensions and Hi ion concentrations, and assessed the effects on PpIX generation and PDT sensitivity. PpIX production was reduced at 0%, 2. 5% (19 mmHg) and 5% (38 mmHg) oxygen compared with that at 21% (160 mm Hg) oxygen (0.15, 0.28 and 0.398 ng mu g(-1) protein compared with 0.6 8 ng mu g(-1) respectively; P < 0.05). The response to PDT was abolish ed by hypoxia, as a result of both reduced PpIX synthesis and reduced PDT toxicity. PpIX production was greater at pH 7.0 and 6.5 (0.75 and 0.66 ng mu g(-1)) compared with that at pH 7.4 and 5.5 (0.41 and 0.55 ng mu g(-1) respectively). PDT cytotoxicity was enhanced at lower pH v alues. These results suggest that ALA-induced PDT may be inhibited by hypoxia due to reduced intrinsic PpIX synthesis. Acidosis may slightly enhance the efficacy of ALA-induced PDT.