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 |
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| Authors: | N. J. de Mol G. M. J. Beijersbergen van Henegouwen B. Weeda C. N. Knox T. G. Truscott |
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| Affiliation: | Department of Pharmacochemistry, Subfaculty of Pharmacy, Gorlaeus Laboratories, State University of Leiden, P.O. Box 9502, 2300 RA Leiden, The Netherlands;department of Chemistry, Paisley College, PA1 2BE, Paisley, Scotland, UK |
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| Abstract: | 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. |
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