Cutaneous photosensitization by 8-methoxypsoralen: order-dependent synergism between radiation less than 380 nm and broadband UVA.

Human skin treated with topical 8-methoxypsoralen (8-MOP) was exposed sequentially to radiation at wave-lengths 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 greater than 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 greater than 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 greater than 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.