PHOTOBINDING OF PSORALENS TO BACTERIAL MACROMOLECULES IN SITU AND INDUCTION OF GENETIC EFFECTS IN A BACTERIAL TEST SYSTEM. EFFECTS OF SINGLET OXYGEN DIAGNOSTIC AIDS D2O AND DABCO

The photobinding of radiolabeled psoralen and 8‐methoxypsoralen (8‐MOP) to biological macromolecules under conditions that affect the lifetime of singlet oxygen (1O2) is reported. These conditions are: increase of 1O2 lifetime in D2O and 1O2 quenching with DABCO. The photobinding to calf thymus DNA was studied in vitro and the covalent photobinding to DNA and other biological macromolecules (RNA, proteins) was also studied in intact bacteria. The results of the DNA photobinding experiments have been related to the induction of genetic damage in a bacterial test system. In addition, laser flash photolysis has been used to measure the effect of D2O and DABCO on the psoralen and 8‐MOP triplet lifetimes. In general D2O increases the triplet lifetimes and DABCO quenches the triplet states with the probable formation of radicals. The results suggest that the covalent photobinding of 8‐MOP to various biological macromolecules in situ is a basis for cell damage occurring at various cellular targets. Analysis of the results of the mutagenicity test suggests that in the presence of D2O the mechanism of induction of genetic lesions is not changed and therefore largely seems to be independent of singlet oxygen.

[1]  W. Wamer,et al.  IN VIVO PROTECTIVE EFFECT OF β‐CAROTENE AGAINST PSORALEN PHOTOTOXICITY , 1985 .

[2]  M. Rodgers,et al.  TIME-RESOLVED LUMINESCENCE MEASUREMENTS OF TRIPLET-SENSITIZED SINGLET-OXYGEN PRODUCTION: VARIATION IN ENERGY-TRANSFER EFFICIENCIES , 1984 .

[3]  M. Granger,et al.  PHOTOADDITION OF 8‐METHOXYPSORALEN TO E. coli DNA POLYMERASE I. ROLE OF PSORALEN PHOTO‐ADDUCTS IN THE PHOTOSENSITIZED ALTERATIONS OF POL I ENZYMATIC ACTIVITIES , 1983, Photochemistry and photobiology.

[4]  G. Moreno,et al.  PHOTODYNAMIC EFFECTS INDUCED BY FUROCOUMARINS ON A MEMBRANE SYSTEM. COMPARISON WITH HEMATOPORPHYRIN , 1982, Photochemistry and photobiology.

[5]  F. Veronese,et al.  THE EFFECT OF PSORALENS AND ANGELICINS ON PROTEINS IN THE PRESENCE OF UV‐A IRRADIATION , 1981, Photochemistry and photobiology.

[6]  G. B. V. Beijersbergen van Henegouwen,et al.  On the involvement of singlet oxygen in mutation induction by 8-methoxypsoralen and UVA irradiation in Escherichia coli K-12. , 1981, Mutation research.

[7]  S. Lerman,et al.  THE PHOTOREACTIONS OF 8‐METHOXYPSORALEN WITH TRYPTOPHAN AND LENS PROTEINS* , 1980, Photochemistry and photobiology.

[8]  M. Artuc,et al.  Reversible binding of 5‐ and 8‐methoxypsoralen to human serum proteins (albumin) and to epidermis in vitro , 1979, The British journal of dermatology.

[9]  B. Bridges,et al.  Mutation induction and killing of Escherichia coli by DNA adducts and crosslinks: a photobiological study with 8-methoxypsoralen. , 1979, Chemico-biological interactions.

[10]  F. Veronese,et al.  Drug-protein interaction: plasma protein binding of furocoumarins. , 1979, Il Farmaco; edizione scientifica.

[11]  K. Yoshikawa,et al.  PHOTO‐CONJUGATION OF 8–METHOXYPSORALEN WITH PROTEINS , 1979 .

[12]  E. Ben-hur,et al.  PHOTOCHEMICAL REACTIONS OF CHLORPROMAZINE; CHEMICAL AND BIOCHEMICAL IMPLICATIONS , 1978, Photochemistry and photobiology.

[13]  H. Singh,et al.  SINGLET OXYGEN: A MAJOR REACTIVE SPECIES IN THE FUROCOUMARIN PHOTOSENSITIZED INACTIVATION OF E. COLI RIBOSOMES , 1978, Photochemistry and photobiology.

[14]  G. Rassner,et al.  Effects of 8-methoxypsoralen plus 365 nm UVA light on Candida albicans cells , 1978, Archives of Dermatological Research.

[15]  S. Cannistraro,et al.  ESR and optical absorption evidence for free radical involvement in the photosensitizing action of furocoumarin derivatives and for their singlet oxygen production. , 1977, Biochimica et biophysica acta.

[16]  G. R. Nakamura Microdetermination of phosphorus. , 1952 .

[17]  Oliver H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[18]  E. Horning,et al.  Furocoumarin Studies. Synthesis of Psoralene and Related Furocoumarins1 , 1950 .

[19]  E. Horning,et al.  Furocoumarins; synthesis of 2,3-dihydropsoralene. , 1948, Journal of the American Chemical Society.

[20]  J. Cadet,et al.  Photoreactions of Furocoumarins (Psoralens and Angelicins) , 1985 .

[21]  M. Pathak,et al.  The nature and molecular basis of cutaneous photosensitivity reactions to psoralens and coal tar. , 1983, The Journal of investigative dermatology.

[22]  J. Lemaire,et al.  Propriétés photosensibilisatrices des furocoumarines IV — Etude photochimique des furocoumarines méthoxylées en solution aqueuse , 1981 .

[23]  G. Wennersten Membrane damage caused by 8-MOP and UVA-treatment of cultivated cells. , 1979, Acta dermato-venereologica.

[24]  R. S. Sinclair,et al.  Triplet states of copper and metal-free phthalocyanines , 1978 .

[25]  D. Goodhead,et al.  The relation between induced mutation frequency and cell survival--a theoretical approach and an examination of experimental data for eukaryotes. , 1977, Mutation research.