Parrish J A, Chylack L T, Woehler M E, Cheng H M, Pathak M A, Morison W L, Krugler J, Nelson W F
J Invest Dermatol. 1979 Sep;73(3):250-5. doi: 10.1111/1523-1747.ep12514338.
Four groups of female Dutch-belted rabbits (Oryctulagus cuniculus) were given methoxsalen (12 mg/kg) or placebo by oral intubation and 1 hr later were exposed to UVA for either 2 or 8 hr. This procedure was repeated 5 days each week for 18 mo. A fifth group received no drug and no UVA exposure. The skin of the animals given methoxsalen and UVA showed signs of acute and chronic phototoxicity. Multiple peripheral blood parameters of hepatic, renal and hematologic function were normal and were not different between groups. Complete ophthalmoscopic examinations were performed periodically. No cataracts were seen in any of the animals. This data provides the perspective that in one species the daily dose of methoxsalen and UVA required to induce chronic cutaneous photosensitization is lower than the daily dose required to induce cataracts. It is inadvisable to interpret this data as suggesting that no risk exists for patients being treated with oral methoxsalen photochemotherapy. The experimental evidence supporting photosensitization as a cause of cataracts and implicating a role of lens DNA in this cataractogenesis is reviewed. Because methoxsalen-UVA alterations of lens DNA or protein could lead to delayed onset of cataracts, and because of the serious nature and potential preventability of phototoxic lens opacification, appropriate protective eye wear is recommended for all patients receiving oral psoralen photochemotherapy.
将四组雌性荷兰带兔（穴兔）通过口服插管给予甲氧沙林（12毫克/千克）或安慰剂，1小时后暴露于紫外线A下2小时或8小时。每周重复此程序5天，持续18个月。第五组未接受药物且未暴露于紫外线A。给予甲氧沙林和紫外线A的动物皮肤出现急性和慢性光毒性迹象。肝脏、肾脏和血液学功能的多个外周血参数正常，且各组之间无差异。定期进行全面的眼科检查。所有动物均未出现白内障。该数据表明，在一个物种中，诱导慢性皮肤光敏化所需的甲氧沙林和紫外线A的每日剂量低于诱导白内障所需的每日剂量。将此数据解释为表明接受口服甲氧沙林光化学疗法的患者不存在风险是不可取的。综述了支持光敏化作为白内障病因以及暗示晶状体DNA在这种白内障形成中起作用的实验证据。由于甲氧沙林-紫外线A对晶状体DNA或蛋白质的改变可能导致白内障延迟发生，并且由于光毒性晶状体混浊的严重性和潜在可预防性，建议所有接受口服补骨脂素光化学疗法的患者佩戴合适的防护眼镜。
