INHIBITION OF SMOOTH-MUSCLE CELL-PROLIFERATION BY VISIBLE LIGHT-ACTIVATED PSORALEN

The present study was designed to evaluate the effect of 8-methoxypsor alen (8-MOP) activated with visible light (419 nm) on the suppression of smooth muscle cell (SMC) proliferation in vitro. We hypothesize tha t if visible light (VL) instead of UVA is used to photoactivate 8-MOP, cytotoxic 8-MOP-DNA cross-link formation can be minimized. Bovine aor ta SMCs (2x10(4)/cm(2)) were incubated with 8-MOP (1 mu g/mL) for 30 m inutes (in the dark) and exposed to a range of VL (2 to 69 J/cm(2)) to determine the dose of VL that inhibits SMC proliferation with minimal toxicity. The results show that 8-MOP in combination with 2 to 12 J/c m(2) VL reversibly inhibited SMC proliferation for up to 5 days after treatment. SMC viability was confirmed by trypan blue exclusion. 8-MOP in combination with 23- or 69-J/cm(2) VL irreversibly inhibited SMC p roliferation. In cell cycle studies, 12-J/cm(2) VL was used to activat e 8-MOP. A phase-specific G(2) blockade that correlated temporally wit h recovery of SMC replication was observed. Photoadduct repair studies showed that cell proliferation rates recovered when 60% of the adduct s had been removed. These results demonstrate for the first time the p ossibility of using VL to activate 8-MOP to inhibit cell proliferation and suggest that 8-MOP/VL photochemotherapy can be used to control SM C growth.