Psoralen-containing sunscreen induces phototoxicity and epidermal ornithine decarboxylase activity

Sunscreens containing 5-methoxypsoralen (5-MOP) are being promoted commercially to increase suntanning and sun protection. A recent study indicated that the 5-MOP concentration used in these sunscreens is too low to induce cutaneous phototoxicity with ultraviolet (UV) radiation. We investigated whether the sunscreen Sun System III (SS III), which contains 5-MOP, could induce skin erythema, edema, delayed pigmentation, and epidermal ornithine decarboxylase (ODC) activity when used in conjunction with UVA radiation (320-400 nm). ODC induction is an early event in the promotion of skin tumors. Increased epidermal ODC activity has been reported after exposure to UVB radiation (290-320 nm) alone and with topical 8-methoxypsoralen (8-MOP) plus UVA radiation. Using a solar simulator, we found SS III-induced erythema, edema, and epidermal ODC activity in hairless mouse skin with only 5 joules/cm2 of UVA. Human skin showed erythema and delayed pigmentation with SS III plus 20 joules/cm2 of UVA. No phototoxicity was seen in human skin unless the solar simulator output was filtered through water to reduce infrared radiation. This indicates that cutaneous phototoxic reactions to 5-MOP plus UVA are diminished by heat. Like 8-MOP, 5-MOP cross-links DNA and has the same skin photocarcinogenic potential as 8-MOP. Therefore the use of phototoxic psoralens in over-the-counter sunscreens is inappropriate because of the risk of increased UV-induced skin cancer.