<title>Exogenous delta-animolevulinic acid induces the porphyrin biosynthesis in human skin organ cultures with different porphyrin patterns in normal and malignant human tissue</title>

Abstract

The carboxylation state of porphyrin metabolites causes their hydrophilic or lipophilic properties and subsequently their distribution in tissues, cells and subcellular compartments. The profile of porphyrin metabolites neither in normal skin nor in malignant skin tumors after administration of 6-aminolevulinic acid has been studied in detail, yet. Explant cultures of normal skin and neoplastic tissues, e.g. keratoakanthoma and basal cell carcinoma, were incubated with 1 mM ALA for 36 h. Total porphyrin concentration and percentage of porphyrin metabolites were determined quantitatively in tissues and corresponding supernatants. 70 -90 % of total porphyrins could be detected in the supernatants of all samples. The highly carboxylated porphyrins were the prevailing metabolites in the supernatants as well as in the tissues. The basal cell carcinoma produced significantly more protoporphyrin and the keratoakanthoma significantly more corpoporphyrin as compared to normal skin. The results show that explant cultures offer an easy approach to examine the enzymatic capacity in porphyrin biosynthesis of various tissues. Benign and malignant human tissues produce different porphyrin metabolites, which may be useful for selective and more effective photodynamic diagnosis or therapy.

Porphyrin concentrations in various human tissues

“…This tneans that none of these lissues are basically enriched wilh porphyrins which would allow one lo perform photodynatnic therapy without exogenous additioti of a pholosensitizer. However, in isolated tumor cells iti vitro atid /'/; vivo, or in hutnan tutnors, an increased seleclive formation of porphyrins with distinctive amounls could be demonstrated afler exogenous addition of 5-aminolevulinic acid (22). These different resulls in tnalignatit lissues may be explaitied by higher rates of tnelabolistn in tutnor cells as well as possible cnzytnatic blocks iti the porphyrin biosynthesis in tutnor cells.…”