SUPPRESSION OF DELAYED-TYPE HYPERSENSITIVITY AND HEMOLYSIS INDUCED BYPREVIOUSLY PHOTOOXIDIZED PSORALEN - EFFECT OF FLUENCE RATE AND PSORALEN CONCENTRATION

The kinetics of the formation of biologically active psoralen photooxi dation (POP) products were analyzed by the biological effects produced , Effects of the UV light fluence rate and psoralen concentration duri ng the preirradiation were investigated to assess the yield of POP pro ducts, which were active in vivo (inducing suppression of delayed-type hypersensitivity [DTN] reaction to sheep red blood cells) and in vitr o (altering the human erythrocyte membrane permeability), It was shown that the reciprocity law of the irradiation fluence rate and time was not valid in the case of POP-induced hemolysis and DTH suppression, I mmunosuppressive POP products were more efficiently formed at low flue nce rate (20.8 W/m(2)), whereas POP hemolysins were more efficiently p roduced at a high fluence rate (180 W/m(2)) of UV light, The yield of immunosuppressive POP products was enhanced in dilute psoralen solutio ns, while the POP hemolysins yield increased with increasing psoralen concentration, A kinetic scheme for psoralen photoproduct formation wa s proposed, Kinetic analysis showed that a labile intermediate was pro duced as the result of excitation of psoralen, This intermediate was e ither converted to a stable immunosuppressive POP product, or two inte rmediates combined to form a POP hemolysin. It is proposed that PUVA t herapy conditions are more favorable for the formation of immunosuppre ssive rather than membrane-damaging psoralen photooxidation products.