Prolonged skin photosensitization induced by methoxsalen and subphototoxic UVA irradiation.

Topical 8-methoxypsoralen (8-MOP) was used to briefly provide free psoralen sufficient for marked cutaneous photosensitization, but only a small dose of UVA was delivered initially, in an effort to produce many monoadducts but few crosslinks. After ample time for clearance of the remaining free psoralen a second UVA exposure was delivered. The second exposure should not have generated any additional monoadducts in the absence of free psoralen, but the remaining monoadducts could be converted to crosslinks. The observation of a prolonged persistent UVA-photosensitive state caused by prior, very small doses of UVA given while free 8-MOP was present strongly suggests that psoralen-DNA crosslinks per se initiate much of the phototoxic effect of 8-MOP on skin, and that monoadducts induce much less acute inflammatory response. Because erythema was studied as the end point, the data say nothing about relative contributions of monoadducts vs crosslinks in causing mutagenesis, hyperpigmentation, therapeutic or other cutaneous responses. Other explanations for the induced persistent photosensitive state are also possible, but less tenable or entirely hypothetical.