Aubin F, Humbert P, Agache P
Department of Functional Dermatology, University Hospital, Besançon, France.
J Dermatol Sci. 1994 Jun;7(3):176-84. doi: 10.1016/0923-1811(94)90093-0.
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)
5-geranoxypsoralen(5-GOP),通常称为佛手柑内酯,是一种高度光反应性的补骨脂素,与大多数呋喃香豆素不同,它与DNA的相互作用不强。5-GOP为以更具选择性的方式研究补骨脂素和UVA辐射诱导的光毒性和免疫活性机制提供了机会。我们研究了5-GOP加UVA辐射(320 - 400nm)重复处理对ATP酶阳性表皮朗格汉斯细胞数量以及光反应性诱导的影响。将这些影响与8-甲氧基补骨脂素(8-MOP)或5-甲氧基补骨脂素(5-MOP)加UVA辐射以及单独UVA辐射的影响进行了比较。C3H/HeN小鼠每周局部外用补骨脂素3次,连续4周,每次随后给予1J/cm²的UVA辐射。在处理结束时,用8-MOP或5-MOP加UVA辐射处理的小鼠表现出严重的总体光毒性,且ATP酶染色的朗格汉斯细胞几乎完全耗竭。两种处理均使朗格汉斯细胞产生严重的形态学改变。5-GOP加UVA辐射处理后未观察到总体但有微观的光毒性作用,而ATP酶阳性朗格汉斯细胞的数量也大大减少。有趣的是,与8-MOP或5-MOP加UVA辐射处理相反,后一种处理未诱导剩余朗格汉斯细胞的形态学改变。我们得出结论,5-GOP加UVA辐射处理后观察到的光毒性和ATP酶染色的表皮免疫细胞数量减少与补骨脂素的DNA结合活性无关。(摘要截短于250字)