Relationship of delta-aminolevulinic acid-induced protoporphyrin IX levelsto mitochondrial content in neoplastic cells in vitro

Protoporphyrin IX, induced by the exogenous addition of delta-aminolevulini c acid, reaches different levels in different tumor cells. Because many of the steps in heme biosynthesis, of which protoporphyrin IX is penultimate, are located in the mitochondria, we surmised that the mitochondrial content of cells may relate to the amount of protoporphyrin IX synthesized in resp onse to excess delta-aminolevulinic acid. We observed that accumulation of MitoTracker, a fluorescent mitochondrial probe, delta-aminolevulinic acid-i nduced protoporphyrin IX levels, and porphobilinogen deaminase activity all presented with the same cell-line-dependent rank order among the four diff erent neoplastic cells. This rank order, however, differed for cytochrome c oxidase activity, the final enzyme in mitochondrial electron transport, an d for accumulation of radioactive label from [C-14]delta-aminolevulinic aci d. The data demonstrate that enzymes involved in heme biosynthesis, in gene ral, display a rank order associated with mitochondrial content. These data imply that such parameters may have value as prognosticators of cells to p roduce delta-aminolevulinic acid-induced protoporphyrin IX, a photosensitiz er for photodynamic therapy of cancer. (C) 1999 Academic Press.