Tumors of the skin in the HRA/Skh mouse after treatment with 8-methoxypsoralen and UVA radiation

Abstract

8-Methoxypsoralen (8-MOP) with and without UVA radiation was administered to HRA/Skh mice (36 animals per treatment group) three times a week in the feed for a total dose of 9-80 mg/kg/week for 52 weeks. Most of the animals at the top dose of 8-MOP with UVA radiation had developed skin toxicity and/or skin tumors by 52 weeks. The skin lesions seen after treatment with 8-MOP and UVA radiation were characterized as squamous cell hyperplasia, squamous cell papilloma, and squamous cell carcinoma and are similar to what has been reported in humans after exposure to 8-MOP and UVA. Squamous cell hyperplasia and acute inflammation of the cornea were also seen in some of the treated female mice. Oral administration of 8-MOP and UVA did not result in a carcinogenic response to other organ systems. There were no increases in skin neoplasms after 8-MOP or UVA radiation alone. 8-MOP given in combination with UVA was carcinogenic to the skin of mice at dose levels similar to those used to treat psoriasis in humans.