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The photoactivation of 8-methoxypsoralen (8-MOP) by ultraviolet light is widely used for the treatment of several skin diseases. The major mechanism is the intercalation of 8-MOP into nuclear DNA in the dark and subsequently the formation of monoadducts and potential cross links under UVA irradiation. In addition, the irradiation of 8-MOP leads to the generation of singlet oxygen by means of photodynamic action which has been shown to induce a critical oxidative damage of the DNA in vitro. To assess the role of singlet oxygen generated by photoactivated 8-MOP, its relaxation in solutions of deuterium oxide was studied in detail. Relaxation rates and rate constants of the involved 8-MOP triplet T1 state and oxygen ¹Δg state were determined by analyzing the rise and decay rates of the luminescence of singlet oxygen at 1.27 μm. The efficacy of singlet oxygen generation is described by the singlet oxygen quantum yield ΦΔ, which depends on the efficacy of 8-MOP T1 state deactivation by oxygen, PT([O2]). PT([O2]) has been determined for different oxygen concentrations and decreased from 2% under aerated conditions (e.g., in vitro conditions, 130 Torr) to 0.5% for the in vivo situation inside the skin (~20 Torr). The efficacy of singlet oxygen generation and maybe therefore the role of singlet oxygen in the oxidative damage depends critically on the respective oxygen partial pressure. This must be considered when transferring results and conclusions from experiments in vitro or in solution to the situation in vivo.

Background: Surveillance of patients with Barrett's esophagus or ulcerative colitis for dysplasia is confined to biopsy specimens taken randomly during endoscopy because dysplasia remains undetectable by visual inspection. We attempted to visualize dysplastic tissue during endoscopy after sensitization with 5-aminolevulinic acid (5-ALA) leading to accumulation and formation of protoporphyrin IX and induction of characteristic red fluorescence of the latter substance using blue light illumination. Methods: Six patients with histologically proven low- or high-grade dysplasia (Barrett's esophagus 2, ulcerative colitis 1, Billroth-II stomach 1, rectal polyps 2) were treated with oral administration of different concentrations of 5-ALA (10 to 20 mg/kg) or by local instillation of 3 gm 5-ALA in the rectum. Endoscopic fluorescence detection was performed 1 to 6 hours after sensitization using a blue light source and compared with conventional white light endoscopy. Biopsies of fluorescent and nonfluorescent areas were compared with histologic findings. Results: Normal duodenal mucosa and squamous epithelium showed more intense 5-ALA-induced background red fluorescence compared with normal mucosa in the stomach or Barrett's mucosa. Histologically, dysplasia was exclusively found in areas with red fluorescence. False-positive fluorescence was associated with microscopic inflammation of the mucosa or feces in the colon. Conclusions: 5-ALA-induced protoporphyrin IX fluorescence may be useful in the detection of dysplasia in the gastrointestinal tract by enhancement of endoscopic surveillance of patients at a high risk for dysplasia.