Toxicity of 8-methoxypsoralen, 5-methoxypsoralen, 3-carbethoxypsoralen, or 5-methylisopsoralen with ultraviolet radiation in the hairless (HRA/Skh) mouse

Abstract

An experimental design to simulate PUVA therapy (oral 8-methoxypsoralen followed by uv radiation) has been tested in a 13-week subchronic study to determine the relative toxicities of 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), 5-methylisopsoralen (5-MIP), and 3-carbethoxypsoralen (3-CEP) in inbred hairless mice (HRA/Skh). Drug was administered by 1-hr pulse feedings three times a week after mice were fasted overnight; individually housed animals were then exposed to uv radiation (320-400 nm; less than 2% output less than 320 nm). 8-MOP or 5-MOP administered orally (at doses of approximately 240 or 480 mg/m2 body surface area per week) followed one-half hour later with uv radiation of 2 J/cm2 for 13 weeks were found to cause skin toxicity including inflammation, hyperplasia, ulceration, and cellular atypia. Dose-related toxicity was not seen in other organ systems. Corresponding levels of 5-MIP or 3-CEP with uv radiation did not produce skin toxicity. These studies show that the psoralens with two potential DNA-binding sites (8-MOP and 5-MOP) were more toxic than psoralens with only one photoreactive site (5-MIP and 3-CEP).