Cutaneous Photosensitization by 8-Methoxypsoralen: Order-Dependent Synergism Between Radiation >380 nm and Broadband UVA

Human skin treated with topical 8-methoxypsoralen (8-MOP) was exposed sequentially to radiation at wavelengths longer than 380 nm and to broadband UVA (320–400 nm). A striking, order-dependent synergism with respect to the induction of cutaneous phototoxicity as measured by delayed erythema was present. When exposure to > 380 nm radiation preceded exposure to broadband UVA, the effect was synergistic. When the order was reversed, the effect was approximately additive. This synergism is best explained by UVA-induced conversion to DNA cross-links of the monoadducts formed by prior exposure at > 380 nm. The direct implication is that cross-linking of DNA by psoralen is the major important event in cutaneous phototoxicity due to psoralens. Skin treated with 8-MOP and markedly suberythemogenic doses of radiation > 380 nm remained synergistically sensitized to small doses of UVA for at least 72 h, long after photosensitization by 8-MOP alone had disappeared in control sites. This suggests slow in vivo repair of those psoralen-DNA monoadducts capable of being subsequently converted to DNA cross-links.