Molecular aspects of extracorporeal photochemotherapy

8-methoxypsoralen (8-MOP), activated upon exposure to long-wavelength ultraviolet radiation, is used therapeutically to treat the diseased blood cells of cutaneous T-cell lymphoma patients. The factors responsible for the efficacy of this therapy are reviewed. Primary among these are the plasma level of 8-MOP at the time of irradiation and the effective dose of UVA. 8-MOP plasma levels determined in a series of six patients demonstrated that the drug is absorbed at a highly variable rate (122 ng/ml +/- 67). A new liquid form of 8-MOP is absorbed with a modest increase in plasma levels (170 ng/ml) but with no improvement in the variability (+/- 163). An examination of the dose-response relationship between 8-MOP concentration and UVA dose indicated that properties such as 8-MOP photoadduct formation and PHA response are proportional to the combined doses of these two factors. A new molecular target for 8-MOP photomodification, cell membrane DNA, is described.