Photobiological activity of suction blister fluid from patients treated with 8-methoxypsoralen.
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.
D001682:Biological Availability; D005110:Extracellular Space / Q000378:metabolism*; D006801:Humans; D008730:Methoxsalen / Q000378:metabolism* / Q000494:pharmacology; D009154:Mutation; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics; D014466:Ultraviolet Rays
D008730:Methoxsalen