title: Products of psoralen photooxidation possess immunomodulative and antileukemic effects.
abstract: It has been proposed that the therapeutic effect of PUVA (psoralens+UVA radiation) is connected to its immunomodulative properties, and that the molecular basis of such properties is the oxygen-independent photoaddition of psoralens to DNA. We have investigated effects of preliminary photooxidized psoralens (POP) on the delayed-type hypersensitivity reaction (DTH) to sheep red blood cells and on growth of grafted T-cell lymphoma EL-4 in mice. We have shown that intravenous injection of POP at low concentrations activated, and at high concentrations suppressed, DTH. The POP products are thermolabile. They preserved their immunosuppressive activity for 3 days at room temperature and lost it in several min at 58 degrees C. Incubation of POP in the presence of Fe2+ during 2 h before intravenous injection leads to complete loss of its immunomodulative activity, suggesting a peroxidic nature of POP products. The POP-inhibited growth of grafted T-cell lymphoma independent of the mode of POP application in mice (intravenous or subcutaneous injections, oral or nasal administration). Our data suggest that photooxidative reactions of psoralens, in addition to oxygen-independent photoaddition to DNA, form the basis for biological activity of these drugs.
authors.affiliation: Department of Medical and Biological Physics, Russian State Medical University, Moscow.
authors.lastname: Potapenko AYa
authors.forename: A A
authors.initials: AA
authors.lastname: Kyagova
authors.forename: L N
authors.initials: LN
authors.lastname: Bezdetnaya
authors.forename: E P
authors.initials: EP
authors.lastname: Lysenko
authors.lastname: Chernyakhovskaya IYu
authors.forename: V A
authors.initials: VA
authors.lastname: Bekhalo
authors.forename: E V
authors.initials: EV
authors.lastname: Nagurskaya
authors.forename: V A
authors.initials: VA
authors.lastname: Nesterenko
authors.forename: N G
authors.initials: NG
authors.lastname: Korotky
authors.forename: S N
authors.initials: SN
authors.lastname: Akhtyamov
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D011564:Furocoumarins / Q000737:chemistry / Q000494:pharmacology* / Q000528:radiation effects; D006968:Hypersensitivity, Delayed; D016399:Lymphoma, T-Cell / Q000188:drug therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D011701:PUVA Therapy; D010777:Photochemistry
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D011564:Furocoumarins