Sequence dependence of benzo[a]pyrene diol epoxide-DNA adduct conformer distribution: A study by laser-induced fluorescence/polyacrylamide gel electrophoresis

Journal Article · · Chemical Research in Toxicology; (United States)

DOI:https://doi.org/10.1021/tx00037a015· OSTI ID:6838730

Marsch, G A; Jankowiak, R; Suh, M; Small, G J ^[1]

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1. Iowa State Univ., Ames, IA (United States)

Low-temperature laser-induced fluorescence techniques in combination with polyacrylamide gel electrophoresis (LIF/PAGE) were used to study the binding of ([minus])-anti- and (+)-anti-benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide (anti-BPDE) to several sequence-defined duplex oligomers. Two of the oligomers contain central 5'-RAGGAR-3' sequences (R = purine) which appear to be frequently mutated by racemic ([+-])-anti-BPDE in endogenous genes of cells cultured in vitro. Two contain a central 5'-CCGG-3' or 5'-TGGT-3' sequence which are strongly preferred for covalent binding but appear to be not so frequently mutated. Binding of the two enantiomers to the latter two sequences yielded a distribution of BPDE-N[sup 2]dG adduct conformations similar to those from binding to highly polymerized, random sequence DNA in vitro which, for ([+-])-anti-BPDE, means that the helix-external conformation of the N[sup 2]-dG adduct is dominant. Binding of ([minus])-anti-BPDE to the 5'-RAGGAR-3' sequences yielded more partially base-stacked and less base-stacked (quasi-intercalated) conformer than observed for random sequence DNA. Importantly, the (+)-anti-BPDE in binding to the more mutagenically inclined 5'-RAGGAR-3' sequences yielded little external-type adduct in comparison to the other two sequences and random sequence DNA. Moreover, an unusually high proportion of the (+)-anti-BPDE adducts formed with the 5'-RAGGAR-3' sequences result from cis stereoaddition, which yields a partially base-stacked configuration. Since the (+)-anti-BPDE appears to be more mutagenic, this result suggests a possible role of internal adduct conformations in mutagenesis. 44 refs., 10 figs., 2 tabs.

• OSTI ID: 6838730
• Journal Information: Chemical Research in Toxicology; (United States), Journal Name: Chemical Research in Toxicology; (United States) Vol. 7:1; ISSN 0893-228X; ISSN CRTOEC
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
560300 -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
AROMATICS
BENZOPYRENE
CHEMICAL REACTION KINETICS
CONDENSED AROMATICS
CONFIGURATION
DNA ADDUCTS
DNA SEQUENCING
ELECTROPHORESIS
EMISSION SPECTROSCOPY
EPOXIDES
FLUORESCENCE SPECTROSCOPY
HYDROCARBONS
KINETICS
MOLECULAR STRUCTURE
MUTAGENESIS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
REACTION KINETICS
SPECTROSCOPY
STRUCTURAL CHEMICAL ANALYSIS