In photodynamic therapy with topically applied delta-aminolevulinic acid porphyrins are acting as photosensitizers. The profile of porphyrin metabolites in normal or in neoplastic skin after administration of delta-aminolevulinic acid has not been determined in detail yet. Thus, to study porphyrin biosynthesis in human skin an organ culture model was developed. Explant pieces of normal skin, keratoacanthoma, and basal cell carcinoma were incubated with 1 mM delta-aminolevulinic acid for 36 h. Levels of delta-aminolevulinic acid, porphyrins and porphyrin metabolites were measured in tissues and supernatants. After incubation with delta-aminolevulinic acid, higher porphyrin levels were demonstrated in tumors as compared to normal skin. In supernatants, most of formed porphyrins, preferentially highly carboxylated porphyrin metabolites, were measured. The pattern of synthesized porphyrins differed between normal and neoplastic skin explants. In tissues of basal cell carcinomas protoporphyrin was preferentially shown and tissues of keratoacanthomas were characterized by a predominance of coproporphyrin as compared to normal skin. The results show that explant cultures offer an easy approach to examine the porphyrin biosynthesis of various tissues. The tumor-specific delta-aminolevulinic acid metabolism indicates additional porphyrin metabolites such as coproporphyrin apart from protoporphyrin as effective photosensitizers and may offer a novel approach to tumor-selective photodynamic damage.

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.