Fritsch C, Batz J, Bolsen K, Schulte K W, Zumdick M, Ruzicka T, Goerz G
Department of Dermatology, Heinrich Heine University, Duesseldorf, Germany.
Photochem Photobiol. 1997 Jul;66(1):114-8. doi: 10.1111/j.1751-1097.1997.tb03146.x.
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.
在用局部应用的δ-氨基乙酰丙酸进行光动力治疗时，卟啉充当光敏剂。给予δ-氨基乙酰丙酸后，正常皮肤或肿瘤皮肤中卟啉代谢物的情况尚未详细确定。因此，为了研究人体皮肤中的卟啉生物合成，建立了一种器官培养模型。将正常皮肤、角化棘皮瘤和基底细胞癌的外植体碎片与1 mM的δ-氨基乙酰丙酸孵育36小时。测量组织和上清液中δ-氨基乙酰丙酸、卟啉和卟啉代谢物的水平。与正常皮肤相比，用δ-氨基乙酰丙酸孵育后，肿瘤中的卟啉水平更高。在上清液中，测量到了大多数形成的卟啉，优先是高度羧化的卟啉代谢物。正常皮肤和肿瘤皮肤外植体中合成的卟啉模式不同。与正常皮肤相比，基底细胞癌组织中优先显示原卟啉，角化棘皮瘤组织的特征是粪卟啉占优势。结果表明，外植体培养为检查各种组织的卟啉生物合成提供了一种简便的方法。肿瘤特异性的δ-氨基乙酰丙酸代谢表明，除了原卟啉外，其他卟啉代谢物如粪卟啉也是有效的光敏剂，这可能为肿瘤选择性光动力损伤提供一种新方法。
