Psoralen photobiology: recent advances.
Clinical efficacy may arise from psoralen-induced photodamage by the induction of a panoply of biomolecules. In cellular studies with UV or photoactivatable agents, the activation of NF-kappa B, probably the most widely studied transcription factor, occurs after its release from an inhibiting factor, I kappa B. The activation of transcription factors has also been correlated with the UV absorption spectrum of DNA (35). Furthermore, it was shown that the photoadducts do not need to be processed or repaired because transcription factor induction is observed in repair-deficient cells. In these latter cells lower UV doses are required to induce these transcription factors. As a result of transcription factor induction, treated cells may have a greater number of class I molecules on their surface and an altered cytokine profile. It is possible (and likely) that these effects occur in different cells to different extents. The important message is that activational events may occur that could alter the cell's (or cells') ability to regulate a disease process. Many studies have shown that the time frame for this type of damage-induced event may range from seconds to minutes (36). Clearly 8-MOP/UVA-induced events such as those described above could be initiated as the result of a single photochemotherapy session.
Gasparro
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FP
Department of Surgery, Yale University, New Haven, CT 06517, USA. gasparrofp@maspo2.mas.yale.edu
D000818:Animals; D004247:DNA / Q000187:drug effects / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D011564:Furocoumarins / Q000494:pharmacology; D006801:Humans; D020672:I-kappa B Proteins; D008027:Light; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D014466:Ultraviolet Rays
D004268:DNA-Binding Proteins; D011564:Furocoumarins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D016328:NF-kappa B; D017319:Photosensitizing Agents; D004247:DNA