TY - JOUR
T1 - Application of fluorescence and linear dichroism techniques to the characterization of the covalent adducts derived from interaction of (±)-trans-9,10-dihydroxy-anti-11,12-epoxy-9,10,11,12-tetrahydrobenzo[e]pyrene with DNA
AU - Gagliano, Antoine G.
AU - Geacintov, Nicholas E.
AU - Ibanez, Victor
AU - Harvey, Ronald G.
AU - Lee, Hong Mee
N1 - Funding Information:
This investigation was supported by PHS grant number CA20851 awarded by the National Cancer Institute, DHHS, and in part by the Department of Energy Contract DE-ACQ2-78EVO4959 to N.E.G., and Contract No. E(l 1-1)2386 at the Radiation and SoHd State Laboratory at New York University. The preparation of the polycvdic aromatic hydrocarbon metabolites at the University of Chicago was supported by American Cancer Society, Grant BC-132.
PY - 1982
Y1 - 1982
N2 - Spectroscopic techniques including absorption, fluorescence excitation and emission spectra, fluorescence decay profiles (determined by single photon counting techniques), and electric linear dichroism are applied to a study of the conformation of covalent adducts derived from a reaction of 9,10-dihydroxy-11,12-epoxy-9,10,11,12-tetrahydro[e]pyrene (B[e]PDE) with DNA. The characteristics of non-covalent adducts obtained from the intercalative binding of 9,10,11,12-tetrahydroxytetrahydrobenzo[e]pyrene (B[e]PT) (derived from the hydrolysis of B[e]PDE) with DNA are compared to those of the covalent B[e]PDE-DNA adducts. It is shown that there are two types of binding sites in B[e]PDE-DNA adducts: (1) an exterior binding site similar to the one observed with the isomeric 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]PDE)-DNA adducts, and (2) a quasi-intercalative type of binding site in which the properties of the pyrene chromophore are similar to those of an intercalated pyrene moiety, but in which the red shift in the absorption maximum, and fluorescence quenching are less pronounced. This latter conformation is not observed in covalent B[a]PDE-DNA adducts. It is shown that the DNA concentration is an important parameter in determining the relative number of pyrene chromophores at these two binding sites. The extent of covalent binding of B[e]PDE is 4-8 times less than the binding of B[a]PDE to DNA under the same experimental conditions. The reduced reactivity of B[e]PDE is tentatively attributed to steric hindrance due to quasi-diaxial conformations of the two hydroxyl groups in one of the two bay-regions of B[e]PDE.
AB - Spectroscopic techniques including absorption, fluorescence excitation and emission spectra, fluorescence decay profiles (determined by single photon counting techniques), and electric linear dichroism are applied to a study of the conformation of covalent adducts derived from a reaction of 9,10-dihydroxy-11,12-epoxy-9,10,11,12-tetrahydro[e]pyrene (B[e]PDE) with DNA. The characteristics of non-covalent adducts obtained from the intercalative binding of 9,10,11,12-tetrahydroxytetrahydrobenzo[e]pyrene (B[e]PT) (derived from the hydrolysis of B[e]PDE) with DNA are compared to those of the covalent B[e]PDE-DNA adducts. It is shown that there are two types of binding sites in B[e]PDE-DNA adducts: (1) an exterior binding site similar to the one observed with the isomeric 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]PDE)-DNA adducts, and (2) a quasi-intercalative type of binding site in which the properties of the pyrene chromophore are similar to those of an intercalated pyrene moiety, but in which the red shift in the absorption maximum, and fluorescence quenching are less pronounced. This latter conformation is not observed in covalent B[a]PDE-DNA adducts. It is shown that the DNA concentration is an important parameter in determining the relative number of pyrene chromophores at these two binding sites. The extent of covalent binding of B[e]PDE is 4-8 times less than the binding of B[a]PDE to DNA under the same experimental conditions. The reduced reactivity of B[e]PDE is tentatively attributed to steric hindrance due to quasi-diaxial conformations of the two hydroxyl groups in one of the two bay-regions of B[e]PDE.
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U2 - 10.1093/carcin/3.9.969
DO - 10.1093/carcin/3.9.969
M3 - Article
C2 - 7139871
AN - SCOPUS:0020438851
SN - 0143-3334
VL - 3
SP - 969
EP - 976
JO - Carcinogenesis
JF - Carcinogenesis
IS - 9
ER -