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- Eriksson, M., et al.
(författare)
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LOCATION OF EXCIMER-FORMING ADDUCTS OF (+)-ANTI-BENZO A PYRENE DIOL EPOXIDE IN DNA
- 1993
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 115:5, s. 1639-1644
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Tidskriftsartikel (refereegranskat)abstract
- Covalent adducts of the carcinogenic polycyclic aromatic hydrocarbon (+)-anti-benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide ((+)-anti-BPDE) in polynucleotides have been studied by fluorescence spectroscopy. The pyrenyl chromophores of the BPDE adducts, linked by the C10 atom to the exocyclic nitrogen of guanine, interact in the photoexcited state, as evidenced by excimer fluorescence. Strong BPDE excimer fluorescence is observed in the alternating poly(dGdC).poly(dGdC) sequence, whereas it is weak in the homopolymeric poly(dG).poly(dC) and in calf thymus DNA. No excimer fluorescence is observed for the BPDE adducts in poly(dAdC).poly(dGdT) or poly(dAdG).poly(dCdT). It is concluded that the formation of BPDE excimers in polynucleotides requires binding to guanines on different strands on consecutive basepairs. The experimental results are supported by graphics modeling and energy minimization of BPDE adducts in various oligonucleotide sequences. The results show that the most favorable arrangement for excimer formation of the BPDE-dG adducts is in a 5'(dCdG-BPDE).5'(dCdG-BPDE) sequence, where the pyrenyl chromophores interact in the minor groove.
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- Graslund, A., et al.
(författare)
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DYNAMICS OF BENZO A PYRENE DIOL EPOXIDE ADDUCTS IN POLY(DG-DC) . (DG-DC) STUDIED BY SYNCHROTRON EXCITED FLUORESCENCE POLARIZATION ANISOTROPY DECAY
- 1992
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Ingår i: Biophysical Chemistry. - : Elsevier BV. - 1873-4200 .- 0301-4622. ; 44:1, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- Time-resolved fluorescence studies have been performed on (+)-anti-7,8-dihydrodiol-9,10-epoxy-benzo[a]pyrene adducts in double-stranded poly(dG-dC) . (dG-dC). Part of the adduct population gives rise to excimer fluorescence. The heterogeneous fluorescence emission decay curves at 22-degrees-C could be resolved into three components with lifetimes: 0.4 ns, 3 ns and 24 ns for the total fluorescence (monomer and excimer emission), and 0.5 ns, 5 ns and 24 ns, respectively, for excimer emission alone. The relative amplitudes for the longer lifetimes were larger for the pure excimer population than for the mixed population. The fluorescence polarization anisotropy decay curves were resolved into two components of rotational correlation times: 0.4 ns and 25 ns for the total fluorescence and 0.3 ns and 33 ns for the excimer fluorescence. We interpret the two rotational correlation times to correspond to local motion of the adduct and segmental motion of the polynucleotide, respectively.
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- Kim, Seog K., et al.
(författare)
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ENHANCEMENT OF BINDING RATE OF RECA PROTEIN TO DNA BY CARCINOGENIC BENZO A PYRENE DERIVATIVES AND SELECTIVE CHANGE OF ADDUCT CONFORMATION
- 1993
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 14:2, s. 311-313
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Tidskriftsartikel (refereegranskat)abstract
- The association kinetics of RecA protein from Escherichia coli to DNA is strongly enhanced if even a minor fraction of DNA bases has been modified by a carcinogenic (+)-anti metabolite of benzo[a]pyrene (BPDE). The enhancement is much smaller with the less carcinogenic (-)-anti enantiomer of BPDE suggesting the possibility that the RecA protein binds selectively to the proto-oncogenic target. Most importantly, the binding of RecA to DNA modified with the latter enantiomer is found to give rise to a reorganization of this BPDE adduct from an intercalation site into a minor groove site. This indicates that the binding mechanism of RecA is via intercalation of some amino acid moiety, a discovery that could explain the approximately 50% contour length increase of the DNA within its fibrous complex with RecA.
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- Ponten, I., et al.
(författare)
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SPECTROSCOPIC STUDIES OF THE TRANS ADDUCTS DERIVED FROM (+)-ANTI-BENZO A PYRENE-7,8-DIHYDRODIOL-9,10-EPOXIDE AND (-)-ANTI-BENZO A PYRENE-7,8-DIHYDRODIOL-9,10-EPOXIDE AND THE OLIGONUCLEOTIDE 5'-D(CCTATAGATATCC)
- 1994
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 15:10, s. 2207-2213
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Tidskriftsartikel (refereegranskat)abstract
- The oligonucleotide 5'-d(CCTATAGATATCC) has been reacted with the (+)- or (-)-enantiomers of trans-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-and (-)-anti-BPDE respectively]. Consistent with previous studies employing single-stranded oligonucleotides, adduct formation of both anti-BPDE enantiomers preferentially involved trans-addition of the C10 position of the diol-epoxide to the exocyclic nitrogen of deoxyguanosine [in the following abbreviated as (+)-BPDE(t)-N-2-G and (-)-BPDE(t)-N-2-G adducts respectively]. The unmodified or (+)-BPDE(t)-N-2-G-modified oligonucleotide was allowed to form duplexes with the complementary sequence 5'-d(GGATATCTATAGG) or sequences in which C has been replaced with T, G or A and analysed with regard to thermal stability. The presence of a (+)-BPDE(t)-N-2-G adduct in oligonucleotide duplexes substantially decreased the value of the melting point relative to the corresponding unmodified duplex. In mismatched complexes containing the (+)-BPDE(t)-N-2-G adduct, a further decrease in thermal stability was observed. The presence of a (+)-BPDE(t)-N-2-G adduct did not seem to change the extent of hyperchromicity (approximate to 20%) upon melting. 5'-d(GGATATCTATAGG) or strands in which C was replaced with T,G or A were gradually added to (+)- or (-)-BPDE(t)-N-2-G-modified oligonucleotides and the fluorescence emission intensity was determined. In all cases with (+)-BPDE(t)-N-2-G, except when C was replaced with A in the complement, the fluorescence intensity steadily decreased and became constant at equal strand concentrations. When a strand containing A in place of C was gradually added to the (+)-BPDE(t)-N-2-G oligonucleotide, a marked increase in the fluorescence intensity was observed (>3-fold). In contrast, addition of strands containing A, T or G to the (-)-BPDE(t)-N-2-G-modified oligonucleotide increased tbe fluorescence intensity from 1.5- to >5-fold. Addition of the fully complementary sequence to the (-)-BPDE(t)-N-2-G-containing oligonucleotide resulted in reduced fluorescence, however less pronounced than with the (+)-BPDE(t)-N-2-G-modified analogue. Significant changes in spectral properties of the adducts were observed in the duplexes. The absorption and fluorescence excitation maxima of the single-stranded (+)-BPDE(t)-N-2-G-modified oligonucleotide were at 353 nm. Insertion of C or A opposite the adduct caused a significant shift of these maxima to shorter wavelengths (347-348 nm). Addition of acrylamide, a fluorescence quencher, reduced the fluorescence intensity in all cases, but to variable extents. The adducts not quenchable by acrylamide demonstrate spectral properties similar to those of the single-stranded (+)-BPDE(t)-N-2-G-modified oligonucleotide.
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