title: Topical application of 5-aminolevulinic acid, DMSO and EDTA: protoporphyrin IX accumulation in skin and tumours of mice.
abstract: Topical 5-aminolevulinic acid (ALA) application in three different creams was carried out on mice bearing subcutaneously transplanted C26 colon carcinoma. The creams contained (a) 20% ALA alone, (b) ALA with 2% dimethylsulphoxide (DMSO) and (c) ALA, DMSO and 2% edetic acid disodium salt (EDTA). Protoporphyrin IX (PP) production in the tumour and in the skin overlying the tumour was studied by two methods: laser-induced fluorescence (LIF) and chemical extraction. The kinetics of PP production in the skin and in the tumour, as studied by the LIF method, was similar for all three cream preparations. The PP fluorescence intensity in the tissues reached its maximum 4-6 h after application of the creams. Quantitative analysis showed that the PP concentration after treatment was more pronounced in the skin than in the tumour. The efficiency of porphyrin production in the skin by the creams used was in the following order: ALA-DMSO-EDTA > ALA-DMSO > ALA. In the tumour the enhancing effect of DMSO and EDTA on PP accumulation induced by ALA was observed mainly in the upper 2 mm section. However, the concentration of PP in the tumour was found to be approximately the same for ALA-DMSO and ALA-DMSO-EDTA cream combinations. The possible mechanisms of the effect of DMSO and EDTA are discussed.
authors.affiliation: Life Sciences Department, Bar Ilan University, Ramat Gan, Israel.
authors.forename: Z
authors.initials: Z
authors.lastname: Malik
authors.forename: G
authors.initials: G
authors.lastname: Kostenich
authors.forename: L
authors.initials: L
authors.lastname: Roitman
authors.forename: B
authors.initials: B
authors.lastname: Ehrenberg
authors.forename: A
authors.initials: A
authors.lastname: Orenstein
mesh_terms: D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003110:Colonic Neoplasms / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage / Q000494:pharmacology*; D004492:Edetic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011524:Protoporphyrins / Q000032:analysis / Q000378:metabolism*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D013050:Spectrometry, Fluorescence / Q000379:methods; D013997:Time Factors
chemical_list: D011524:Protoporphyrins; D000622:Aminolevulinic Acid; D004492:Edetic Acid; C028025:protoporphyrin IX; D004121:Dimethyl Sulfoxide