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Abstract
5-geranoxypsoralen (5-GOP), commonly called bergamottin, is a highly photoreactive
psoralen, which in contrast to most furocoumarins, does not strongly interact with
DNA. 5-GOP gives the opportunity to study, in a more selective way, the mechanisms
of phototoxic and immunological activities induced by psoralen and UVA radiation.
We investigated the effects of repetitive treatments with 5-GOP plus UVA radiation
(320–400 nm) on the number of ATPase+ epidermal Langerhans cells and on the induction of photoreactivity. These effects
were compared with those of 8-methoxypsoralen (8-MOP) or 5-methoxypsoralen (5-MOP)
plus UVA radiation and UVA radiation alone. ![Math Eq]()
mice were treated topically with the psoralen three times/week for 4 consecutive
weeks followed each time by 1 J/cm2 of UVA radiation. At the end of the treatment, mice treated with 8-MOP or 5-MOP plus
UVA radiation exhibited severe gross phototoxicity and nearly total depletion of ATPase-stained
Langerhans cells. Both treatments produced severe morphological alterations of Langerhans
cells. No gross but a microscopic phototoxic effect was observed after 5-GOP plus
UVA radiation treatment, while the number of ATPase+ Langerhans cells was also greatly reduced. Interestingly the latter treatment induced
no morphological alterations of the remaining Langerhans cells in contrast to treatment
with 8-MOP or 5-MOP plus UVA radiation. We conclude that phototoxicity and decrease
in the number of ATPase-stained epidermal immune cells observed after treatment with
5-GOP plus UVA radiation are not related to the DNA binding activity of the psoralen.
A second type of photoreaction which is oxygen mediated may be involved.
mice were treated topically with the psoralen three times/week for 4 consecutive
weeks followed each time by 1 J/cm2 of UVA radiation. At the end of the treatment, mice treated with 8-MOP or 5-MOP plus
UVA radiation exhibited severe gross phototoxicity and nearly total depletion of ATPase-stained
Langerhans cells. Both treatments produced severe morphological alterations of Langerhans
cells. No gross but a microscopic phototoxic effect was observed after 5-GOP plus
UVA radiation treatment, while the number of ATPase+ Langerhans cells was also greatly reduced. Interestingly the latter treatment induced
no morphological alterations of the remaining Langerhans cells in contrast to treatment
with 8-MOP or 5-MOP plus UVA radiation. We conclude that phototoxicity and decrease
in the number of ATPase-stained epidermal immune cells observed after treatment with
5-GOP plus UVA radiation are not related to the DNA binding activity of the psoralen.
A second type of photoreaction which is oxygen mediated may be involved.Keywords
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References
- Effect of psoralen and ultraviolet radiation on murine dendritic epidermal cells.J Invest Dermatol. 1989; 92: 657-662
- Local suppression of contact hypersensitivity in mice by a new bifunctional psoralen, 4,4′,5′-trimethylazapsoralen, and UVA radiation.J Invest Dermatol. 1991; 97: 50-54
- Mechanisms of psoralen photosensitization reactions.Natl Cancer Inst Monogr. 1984; 66: 41-46
- Photoreactivity of 5-geranoxypsoralen and lack of photoreaction with DNA.Photochem Photobiol. 1991; 53: 13-19
- The photobiological activity of 5-geranoxypsoralen and its photoproducts.Photochem Photobiol. 1992; 55: 529-532
- Cytochemical identification of ATPase-positive Langerhans cells in EDTA-separated sheets of mouse epidermis.Br J Dermatol. 1975; 92: 523-531
- Pertubation of epidermal Langerhans cells in basal cell carcinomas.Am J Dermatopathol. 1987; 9: 465-473
- Immunosuppression in phototherapy.in: Photosensitizing Compounds: their Chemistry, Biology, and Clinical Use. Ciba Foundation Symposium 146. 1989: 131-147 (Chichester, UK)
- In vitro photostability and photosensitizing properties of berganot oil. Effect of cinnamate sunscreen.J Photochem Photobiol B. 1990; 7: 199-208
- Characterization of the steam non-volatile residue of bergamot oil and some other essential oils.J Assoc Off Anal Chem. 1969; 52: 719-728
- A study of oil of bergamot and its importance as a phototoxic agent. I: Characterization and quantification of the photoreactive component.Br J Dermatol. 1977; 96: 475-782
- Phytophotodermatitis.in: Pathak MA Harber LA Seiji M Kukita A Sunlight and Man: Normal and Abnormal Photobiologic Responses. University of Tokyo Press, Tokyo1974: 495-513
- Perfume phototoxicity.J Soc Cosmet Chem. 1970; 21: 695-715
- A possible mechanism of psoralen phototoxicity not involving direct interaction with DNA.in: Proc Natl Acad Sci USA. 82. 1985: 6158-6162
- Chemical mechanism of the bioeffects of furocoumarins: the role of reactions with proteins, lipids and other cellular constituents.in: Gasparo FP Psoralen, DNA, Photobiology. Vol. II. CRC Press, Boca Raton, Florida1988: 1-49
- Relation between some photobiological properties of furocoumarins and their extent of singlet oxygen production.Photochem Photobiol. 1981; 33: 815-819
- Singlet oxygen generation by furocoumarins: effect of DNA and liposomes.Photochem Photobiol. 1987; 45: 177-183
- Recent advances in psoralen phototoxicity mechanisms.Photochem Photobiol. 1989; 50: 859-882
- Effects of a new bifunctional psoralen, 4,4′,5′-trimethylazapsoralen and ultraviolet A radiation on murine dendritic epidermal cells.Photodermatol Photoimmunol Photomed. 1990; 7: 123-127
- 4,4′,5′-trimethyl-8-azapsoralen, a new photoreactive and non-skin-phototoxic bifunctional bioisoster of psoralen.Photochem Photobiol. 1991; 53: 143-148
- Relationship between lesions photoinduced by mono- and bi-functional furocoumarins in DNA and genotoxic effects in diploid yeast.Mut Res. 1985; 151: 217-233
- New psoralen and angelicin derivatives.in: Gasparo FP Psoralen, DNA, Photobiology. Vol. II. CRC Press, Boca Raton, Florida1988: 37-114
Article info
Publication history
Accepted:
December 27,
1993
Received in revised form:
December 24,
1993
Received:
July 12,
1993
Footnotes
☆This work was presented, in part, at the European Society for Dermatological Research, Amsterdam, 3–6 April 1993.
Identification
Copyright
© 1994 Published by Elsevier Inc.
