Ex vivo application of delta-aminolevulinic acid induces high and specific porphyrin levels in human skin tumors: Possible basis for selective photodynamic therapy
Ex vivo application of delta-aminolevulinic acid induces high and specific porphyrin levels in human skin tumors: Possible basis for selective photodynamic therapy
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DOI：
10.1111/j.1751-1097.1997.tb03146.x
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发表时间：
1997-07-01
影响因子：
3.3
通讯作者：
Goerz, G
中科院分区：
文献类型：
--
作者：
Fritsch, C;Batz, J;Goerz, G
在光动力疗法与局部应用的δ-氨基乙酰丙酸卟啉作为光敏剂。在施用δ-氨基乙酰丙酸后，卟啉代谢物在正常皮肤或肿瘤皮肤中的分布尚未详细确定。因此，为了研究人皮肤中卟啉的生物合成，开发了器官培养模型。将正常皮肤、角化棘皮瘤和基底细胞癌的外植体与ImM 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δ-氨基乙酰丙酸孵育后，与正常皮肤相比，在肿瘤中显示出更高的卟啉水平。在上清液中，测量了大多数形成的卟啉，优选高度羧基化的卟啉代谢物。合成的卟啉的模式在正常和肿瘤性的技能外植体之间不同。在基底细胞癌的组织中，优选显示原卟啉，并且表征了角化棘皮瘤的组织。结果表明，外植体培养提供了一种简单的方法来检查各种组织的卟啉生物合成，肿瘤特异性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，并可能为肿瘤选择性光动力损伤提供一种新的方法。
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 skill 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.