Possible mechanism of psoralen phototoxicity not involving direct interaction with DNA
Psoralens in combination with ultraviolet light (UVA; 320-400 nm) are used in the photochemical treatment of a variety of skin diseases including vitiligo, a skin depigmentational disorder, and psoriasis, a disease of accelerated epidermal cell proliferation. Although it is generally assumed that the major site of action of the psoralens is DNA, the authors have obtained evidence that another site may be the primary target for these compounds. They have identified specific, saturable, high-affinity binding sites for 8-methoxypsoralen on HeLa cells and have detected specific binding of 8-methoxypsoralen to four other human cell lines and five mouse cell lines. In HeLa cells, specific binding is reversible and independent of the ability of the compound to intercalate into DNA. In addition, binding sites become covalently modified by the psoralen after UVA exposure. Specific binding of 8-(methyoxy-/sup 3/H)methoxypsoralen constitutes 79% of the label bound to the cells. Scatchard analysis indicated two classes of psoralen binding sites. Based on these findings, the authors hypothesize that specific binding sites for psoralens on mammalian cells mediate, at least in part, psoralen-induced phototoxicity.
- Research Organization:
- Rutgers Univ., Piscataway, NJ
- OSTI ID:
- 6169109
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 82:18
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
PSORALEN
PHOTOCHEMISTRY
TOXICITY
SKIN
RADIOTHERAPY
DNA ADDUCTS
HELA CELLS
NEAR ULTRAVIOLET RADIATION
TRITIUM COMPOUNDS
ADDUCTS
ANTICOAGULANTS
BODY
CHEMISTRY
COUMARINS
DRUGS
ELECTROMAGNETIC RADIATION
HEMATOLOGIC AGENTS
HETEROCYCLIC COMPOUNDS
LABELLED COMPOUNDS
MEDICINE
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
RADIATIONS
RADIOLOGY
THERAPY
ULTRAVIOLET RADIATION
560121* - Radiation Effects on Cells- External Source- (-1987)