CONTROL OF SMOOTH-MUSCLE CELL-PROLIFERATION BY PSORALEN PHOTOCHEMOTHERAPY

Purpose: Restenosis after balloon angioplasty or the intimal hyperplas ia occurring at distal anastomoses of bypass grafts severely limits th e long-term therapy for peripheral vascular disease. The aim of this s tudy was to evaluate the application of psoralen photochemotherapy wit h ultraviolet A (UVA)-activated 8-methoxypsoralen (8-MOP) to suppress smooth muscle cell (SMC) proliferation in vitro by the formation of 8- MOP-DNA monoadducts and interstrand cross-links to inhibit DNA synthes is. Methods: Bovine aorta SMC (2 x 10(4)/cm2) were treated with 8-MOP (0 to 1000 ng/ml) for 30 minutes, followed by UVA (2 joule/cm2) to det ermine the dose of 8-MOP and UVA that inhibits SMC proliferation. Resu lts: The results show that 8-MOP in the range 30 to 1000 ng/ml in comb ination with 2 joule/cm2 UVA inhibited SMC proliferation by 40% to 60% 3 days after treatment. In time course studies the growth of SMC trea ted with 100 ng/ml 8-MOP and 2 joule/CM2 UVA were monitored over 5 day s, and this regimen was found to be cytostatic. SMC viability was conf irmed by trypan blue exclusion. Conclusions: Our studies suggest that 8-MOP/UVA photochemotherapy may represent a novel approach to the cont rol of localized SMC proliferation.