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Photobiological activity of suction blister fluid from patients treated with 8-methoxypsoralen
Abstract:
Suction blister fluid was collected from normal human volunteers before (SBF) and 2 h after (SBF 8-MOP) oral 8-methoxypsoralen (0.6 mg/kg) ingestion without irradiation. In SBF 8-MOP the concentration of 8-MOP was 150 ng/ml, and fluorescent metabolites were also present. The toxicity of SBF 8-MOP was then determined with and without UV-A irradiation in the diploid strain D7 of the yeast Saccharomyces cerevisiae which is suitable for the detection of lethal, mutagenic and recombinogenic events. It was compared with that of SBF, SBF with 8-MOP added in vitro (150 ng/ml) and 8-MOP (150 ng/ml) in water. SBF showed no effect with UV-A doses up to 360 kJ m-2; SBF 8-MOP showed a slight decrease in survival and a dose-dependent increase in nuclear mutations, mitotic gene conversion and crossing over; SBF with 8-MOP added in vitro showed increased photobiological activity compared with SBF 8-MOP. This photobiological activity was increased by a factor of six when using 8-MOP in water. These results indicate a different bioavailability of 8-MOP in water and in interstitial fluid containing proteins. The metabolites of 8-MOP in human skin did not increase the photobiological activity of the drug. We conclude that the 8-MOP present in human skin during PUVA therapy is mutagenic and recombinogenic for eukaryotic cells.
Insights
8-methoxypsoralen (8-MOP) in human skin fluid during PUVA therapy is mutagenic and recombinogenic to yeast cells. Its bioavailability differs in interstitial fluid versus water, with skin metabolites not enhancing phototoxicity.
Area of Science:
- Photobiology
- Toxicology
- Genetics
Background:
- 8-methoxypsoralen (8-MOP) is a photosensitizing agent used in PUVA therapy.
- Understanding 8-MOP's behavior in biological fluids is crucial for assessing its risks.
Purpose of the Study:
- To evaluate the mutagenic and recombinogenic potential of 8-MOP in human suction blister fluid (SBF).
- To compare the phototoxicity of 8-MOP in SBF versus in vitro conditions and water.
Main Methods:
- Collected SBF from volunteers before and after oral 8-MOP administration.
- Assessed toxicity (lethal, mutagenic, recombinogenic events) in Saccharomyces cerevisiae (yeast).
- Compared SBF with 8-MOP to controls and 8-MOP in water under UV-A irradiation.
Main Results:
- 8-MOP in SBF induced mutations, gene conversion, and crossing over in yeast.
- Photobiological activity was higher for 8-MOP in water than in SBF.
- Metabolites of 8-MOP in SBF did not enhance phototoxicity compared to 8-MOP alone.
Conclusions:
- 8-MOP in human skin during PUVA therapy exhibits mutagenic and recombinogenic effects on eukaryotic cells.
- Bioavailability and phototoxicity of 8-MOP are influenced by its presence in interstitial fluid versus aqueous solutions.