The nature and molecular basis of cutaneous photosensitivity reactions to psoralens and coal tar
The basic aspects of cutaneous photosensitization reactions and the mode of therapeutic effectiveness of psoralens and coal tar, the two groups of photosensitizing agents used extensively in the photochemotherapy of psoriasis, have been reviewed. Psoralen-induced skin photosensitization and the therapeutic action of psoralens involve two distinct types of reactions, and these two reactions occur independently of each other and concurrently when the psoralen-treated skin (oral or topical) is exposed to 320 to 400 nm of radiation. The first, type I, is an oxygen-independent reaction and primarily involves photoreaction with DNA; the second, type II, is a sensitized reaction dependent on oxygen and involves the formation of singlet oxygen (1O2). The photoreactive form of psoralen is its triplet state, and the sites of reaction are (1) the cell membrane of the epidermal, dermal, and endothelial cells; (2) the cytoplasmic constituents, such as enzymes, RNA, lysosomes, etc.; (3) the cell nuclei (DNA and chromatin); and (4) the sensitized production of 1O2, which is responsible for cell-membrane damage and vasodilation. The major damage would be initiated by a type I reaction and would be seen in the form of nuclear damage to DNA resulting from the interaction of psoralen with DNA and to a lesser extent with RNA. The skin photosensitization response (erythema, edema, membrane damage, etc.) would result from a type II reaction involving the generation of 1O2. Crude coal tar (CCT), widely used in the Goeckerman therapy for psoriasis, also produces type I and type II reactions. The therapeutic and photosensitizing actions of CCT are due to (1) the photoconjugation of the photoreactive ingredients of CCT with DNA, causing interstrand cross-links; and (2) the production of 1O2. CCT is an efficient producer of 1O2, more so than 8-methoxypsoralen, and is responsible for cell-membrane damage and cellular edema.
- Research Organization:
- Department of Dermatology, Massachusetts General Hospital, Boston
- OSTI ID:
- 5551562
- Journal Information:
- J. Invest. Dermatol.; (United States), Vol. 80
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
COAL TAR
PHOTOCHEMISTRY
PSORALEN
SKIN
PHOTOSENSITIVITY
SKIN DISEASES
CHEMOTHERAPY
CELL MEMBRANES
CELL NUCLEI
DNA
RADICALS
ULTRAVIOLET RADIATION
ANTICOAGULANTS
BODY
CELL CONSTITUENTS
CHEMISTRY
COUMARINS
DISEASES
DRUGS
ELECTROMAGNETIC RADIATION
HEMATOLOGIC AGENTS
HETEROCYCLIC COMPOUNDS
MEMBRANES
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
OTHER ORGANIC COMPOUNDS
RADIATIONS
SENSITIVITY
TAR
THERAPY
550600* - Medicine