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).

journal_name

Toxicol Appl Pharmacol

authors

Dunnick JK,Forbes PD,Davies RE,Iverson WO

doi

10.1016/0041-008x(87)90177-3

subject

Has Abstract

pub_date

1987-06-15 00:00:00

pages

73-80

issue

1

eissn

0041-008X

issn

1096-0333

pii

0041-008X(87)90177-3

journal_volume

89

pub_type

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