TY - JOUR
T1 - Spectroscopic characteristics and site I/site II classification of cis and trans benzo[a]pyrene diolepoxide enantiomer-guanosine adducts in oligonucleotides and plynucleotides
AU - Geacintov, Nicholas E.
AU - Cosman, Monique
AU - Mao, Bing
AU - Alfano, Anna
AU - Ibanez, Victor
AU - Harvey, Ronald G.
N1 - Funding Information:
This research was supported by the Department of Energy, Office of Health and Environmental Research, grant DE-FGO2-86ER60405, and in part by DOE grant DE-FGO2-88ER60674. The DNA and BPDE adduct synthesis is supported by grant CA 20851 from the US Public Health Service, Department of Health and Human Resources, awarded by the National Cancer Institute. At the University of Chicago, this work was supported by the National Institute of Environmental Health Sciences, grant no. ES-04732.
PY - 1991/11
Y1 - 1991/11
N2 - The highly tumorigenic isomer (+)-7,8-dihydroxy-anti-9, 10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE] and its non-tumorigenic enantiomer (-)-anti-BPDE are known to react predominantly with the exocyclic amino group (N2) of deoxyguanine in DNA and to form adducts of different conformations. The spectroscopic characteristics (UV absorbance, fluorescence and circular dichroism) of stereochemically defined (+)-trans, (-)-trans, (+)-cis and (-)-cis d(5'-CACATGBPDETACAC) adducts in the single-stranded form, or complexed with the complementary strand d(5'-GTGTACATGTG) in aqueous solution, were investigated. The spectroscopic characteristics of the double-stranded d(5'-CACATGBPDETACAC)·d(5'-GTGTACATGTG) adducts can be interpreted in terms of two types of conformations. In site I-type conformations, there is an ̃10 nm red shift in the absorption maxima, which is attributed to significant pyrenyl residue-base interactions; in site II-type adducts, the red shift is only ̃2-3 nm, and the pyrene ring system is located at external, solvent-exposed binding sites. The spectroscopic characteristics of the BPDE-modified duplexes are of the site II type for the (+)- and (-)-trans, and of the site I type for the (+)- and (-)-cis adducts. In adducts derived from the binding of (+)-anti-BPDE to poly(dG-dC)·(dG-dC) and poly(dG)·(dC), the trans/cis BPDE-N2-dG adduct ratio is 6 ± 1; in the case of (-)-anti-BPDE this ratio is only 0.4 ± 0.1 and 0.6 ± 0.15 in poly(dG-dC)·(dG-dC) and poly(dG)·(dC) respectively. The spectroscopic properties of these BPDE-modified poly-nucleotide adducts are consistent with those of the BPDE-modified oligonucleotide complexes; the cis adducts are correlated with site I adduct conformations, while the trans adducts are of the site II type. The correlations between adduct characteristics and biological activities of the two BPDE enantiomers are discussed.
AB - The highly tumorigenic isomer (+)-7,8-dihydroxy-anti-9, 10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE] and its non-tumorigenic enantiomer (-)-anti-BPDE are known to react predominantly with the exocyclic amino group (N2) of deoxyguanine in DNA and to form adducts of different conformations. The spectroscopic characteristics (UV absorbance, fluorescence and circular dichroism) of stereochemically defined (+)-trans, (-)-trans, (+)-cis and (-)-cis d(5'-CACATGBPDETACAC) adducts in the single-stranded form, or complexed with the complementary strand d(5'-GTGTACATGTG) in aqueous solution, were investigated. The spectroscopic characteristics of the double-stranded d(5'-CACATGBPDETACAC)·d(5'-GTGTACATGTG) adducts can be interpreted in terms of two types of conformations. In site I-type conformations, there is an ̃10 nm red shift in the absorption maxima, which is attributed to significant pyrenyl residue-base interactions; in site II-type adducts, the red shift is only ̃2-3 nm, and the pyrene ring system is located at external, solvent-exposed binding sites. The spectroscopic characteristics of the BPDE-modified duplexes are of the site II type for the (+)- and (-)-trans, and of the site I type for the (+)- and (-)-cis adducts. In adducts derived from the binding of (+)-anti-BPDE to poly(dG-dC)·(dG-dC) and poly(dG)·(dC), the trans/cis BPDE-N2-dG adduct ratio is 6 ± 1; in the case of (-)-anti-BPDE this ratio is only 0.4 ± 0.1 and 0.6 ± 0.15 in poly(dG-dC)·(dG-dC) and poly(dG)·(dC) respectively. The spectroscopic properties of these BPDE-modified poly-nucleotide adducts are consistent with those of the BPDE-modified oligonucleotide complexes; the cis adducts are correlated with site I adduct conformations, while the trans adducts are of the site II type. The correlations between adduct characteristics and biological activities of the two BPDE enantiomers are discussed.
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U2 - 10.1093/carcin/12.11.2099
DO - 10.1093/carcin/12.11.2099
M3 - Article
C2 - 1934295
AN - SCOPUS:0025991599
SN - 0143-3334
VL - 12
SP - 2099
EP - 2108
JO - Carcinogenesis
JF - Carcinogenesis
IS - 11
ER -