Effects of a new psoralen, 5-geranoxypsoralen, plus UVA radiation on murine ATPase positive Langerhans cells.
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. C3H/HeN 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Aubin
F
F
Department of Functional Dermatology, University Hospital, Besançon, France.
Humbert
P
P
Agache
P
P
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D000078404:Epidermal Cells; D004817:Epidermis / Q000201:enzymology / Q000528:radiation effects; D005260:Female; D011564:Furocoumarins / Q000494:pharmacology / Q000627:therapeutic use*; D007801:Langerhans Cells / Q000166:cytology / Q000201:enzymology* / Q000528:radiation effects*; D051379:Mice; D008809:Mice, Inbred C3H; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D014466:Ultraviolet Rays
D011564:Furocoumarins; D011838:Radiation-Sensitizing Agents; D000251:Adenosine Triphosphatases; C068337:bergamottin