Comparative effect of ALA derivatives on protoporphyrin IX production in human and rat skin organ cultures

Samples of human and rat skin in short-term organ culture exposed to ALA or a range of hydrophobic derivatives were examined for their effect on the a ccumulation of protoporphyrin IX (PpIX) measured using fluorescence spectro scopy. With the exception of carbobenzoyloxy-D-phenylalanyl-5-ALA-ethyl est er the data presented indicate that, in normal tissues, ALA derivatives gen erate protoporphyrin IX more slowly than ALA, suggesting that they are less rapidly taken up and/or converted to free ALA. However, the resultant depo t effect may lead to the enhanced accumulation of porphyrin over long expos ure periods, particularly in the case of ALA-methyl ester or ALA-hexyl este r, depending on the applied concentration and the exposed tissue. Addition of the iron chelator, CP94, greatly increased PpIX accumulation in human sk in exposed to ALA, ALA-methyl ester and ALA-hexyl ester. The effect in rat skin was less marked.