Gange R W, Levins P C, Anderson R R, Parrish J A
J Invest Dermatol. 1984 Jun;82(6):594-7. doi: 10.1111/1523-1747.ep12261365.
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.
用外用8-甲氧基补骨脂素（8-MOP）处理过的人体皮肤依次暴露于波长大于380nm的辐射和宽带紫外线A（320 - 400nm）下。通过延迟红斑测量，在皮肤光毒性诱导方面存在显著的、依赖顺序的协同作用。当在暴露于宽带紫外线A之前先暴露于大于380nm的辐射时，效果是协同的。当顺序颠倒时，效果大约是相加的。这种协同作用最好的解释是紫外线A诱导先前在大于380nm处暴露形成的单加合物转化为DNA交联。直接的含义是补骨脂素对DNA的交联是补骨脂素引起皮肤光毒性的主要重要事件。用8-MOP处理过的皮肤，在接受明显低于致红斑剂量的大于380nm的辐射后，对小剂量紫外线A仍保持协同敏感性至少72小时，而在对照部位，仅用8-MOP进行光致敏后这种敏感性早已消失。这表明那些能够随后转化为DNA交联的补骨脂素 - DNA单加合物在体内修复缓慢。
