Ex vivo application of delta-aminolevulinic acid induces high and specific porphyrin levels in human skin tumors: Possible basis for selective photodynamic therapy

被引:28
作者
Fritsch, C
Batz, J
Bolsen, K
Schulte, KW
Zumdick, M
Ruzicka, T
Goerz, G
机构
[1] Department of Dermatology, Heinrich Heine University, Dusseldorf
[2] Department of Dermatology, Heinrich Heine University, 40225 Duesseldorf
关键词
D O I
10.1111/j.1751-1097.1997.tb03146.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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收藏
页码:114 / 118
页数:5
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