Control of smooth muscle cell proliferation by psoralen photochemotherapy.
OBJECTIVE
Restenosis after balloon angioplasty or the intimal hyperplasia occurring at distal anastomoses of bypass grafts severely limits the long-term therapy for peripheral vascular disease. The aim of this study was to evaluate the application of psoralen photochemotherapy with 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 synthesis.


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 determine the dose of 8-MOP and UVA that inhibits SMC proliferation.


RESULTS
The results show that 8-MOP in the range 30 to 1000 ng/ml in combination with 2 joule/cm2 UVA inhibited SMC proliferation by 40% to 60% 3 days after treatment. In time course studies the growth of SMC treated with 100 ng/ml 8-MOP and 2 joule/cm2 UVA were monitored over 5 days, and this regimen was found to be cytostatic. SMC viability was confirmed by trypan blue exclusion.


CONCLUSIONS
Our studies suggest that 8-MOP/UVA photochemotherapy may represent a novel approach to the control of localized SMC proliferation.
Department of Surgery (Vascular), Yale University School of Medicine, New Haven, CT 06510.
B E
BE
Sumpio
S M
SM
Phan
F P
FP
Gasparro
L I
LI
Deckelbaum
D000818:Animals; D001011:Aorta / Q000737:chemistry; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006965:Hyperplasia / Q000517:prevention & control; D066298:In Vitro Techniques; D008730:Methoxsalen / Q000032:analysis / Q000378:metabolism / Q000627:therapeutic use; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000166:cytology*; D011701:PUVA Therapy
D004247:DNA; D008730:Methoxsalen