Cellular and molecular mechanisms in photochemical sensitization: studies on the mechanism of action of psoralens.

The interaction of chemicals and light to induce sensitization reactions in the skin is a complex multistep process resulting in physiological changes in both the dermal and epidermal cell layers as well as characteristic inflammatory reactions. It is becoming increasingly apparent that an array of growth factors and cytokines acting on different components of the skin are involved in the regulation of these processes. One of the best characterized classes of chemical photosensitizers are the psoralens, a group of compounds that must be activated by UV light in wavelengths ranging from 320 to 400 nm (UVA) to initiate their biological actions. Recent evidence suggests that the ability of the psoralens to induce sensitization reactions, which include alterations in epidermal cell growth and differentiation, is highly specific and due to interactions with the epidermal growth factor (EGF) receptor. Specific receptor proteins for the psoralens have been identified in cytoplasmic and membrane fractions of responsive cells. Binding of psoralens to these proteins is of high affinity and reversible. UVA light causes psoralens to photoalkylate their receptors, a process thought to activate the receptor. One early biochemical event at the cell surface membrane linked to psoralen-receptor activation is the inhibition of EGF binding and alterations in the structure and function of the EGF receptor. These findings suggest that the cell surface membrane is an important target for chemical photosensitizers such as the psoralens. In addition, since photoactivated psoralens modulate epidermal cell growth and differentiation, the ability of these compounds to modify the function of the EGF receptor may underlie their biological activity as chemical photosensitizers.