Effects of a new bifunctional psoralen, 4,4',5'-trimethylazapsoralen and ultraviolet-A radiation on murine dendritic epidermal cells

Although some psoralens are therapeutically active in the treatment of cutaneous hyperproliferative diseases when combined with UVA (320-400 nm) radiation, the toxic effects of these compounds have led physicians to seek new photochemotherapeutic agents. One such agent is 4,4',5'-trimethylazapsoralen (TMAP), a new bifunctional psoralen compound. We investigated the effects of repetitive treatments with TMAP plus UVA radiation on the number of dendritic immune cells in murine epidermis and on the induction of phototoxicity. Mice treated 3 times per week for 4 weeks with 129 microgram TMAP plus 10 kJ/m2 UVA radiation exhibited no gross or microscopic evidence of phototoxicity. During this treatment, the numbers of ATPase+, Ia+, and Thy-l+ dendritic epidermal cells were greatly reduced, and by the end of the treatment period, few dendritic immune cells could be detected. We conclude that morphological alterations of cutaneous immune cells can occur in the absence of overt phototoxicity, and that TMAP plus low-dose UVA radiation decreases the numbers of detectable Langerhans cells and Thy-1+ cells in murine skin.