Base sequence effects on interactions of aromatic mutagens with DNA (deoxyribonucleic acid)
The base-sequence dependence of the adduct conformations-derived from the covalent binding of trans-7,8-diol-anti-9,10--epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE) (+) and (-) enantiomers to synthetic DNAs of defined base composition and sequence is described. The diol epoxide BPDE is the ultimate mutagenic and tumorigenic metabolite of benzo(a)pyrene, a common air pollutant, which is a byproduct of fossil fuel combustion processes. The covalent addition products of BPDE can be classified according to two types: (1) site I, involving carcinogen-DNA base stacking interactions, and (2) site II, in which the BPDE residue appears to be located at a partially external DNA binding site. The presence of site II adducts, rather than site I adducts, is correlated with high mutagenicities and tumorigenicities of polycyclic aromatic diol epoxides. It is shown here that the formation of site II adducts derived from the binding of the more tumorigenic (+)- BPDE enantiomer to DNA is particularly favored in deoxyguanine-rich sequences. 12 refs., 6 figs., 3 tabs.
- Research Organization:
- New York Univ., NY (USA). Dept. of Chemistry
- Sponsoring Organization:
- DOE/ER
- DOE Contract Number:
- FG02-88ER60674
- OSTI ID:
- 5643342
- Report Number(s):
- DOE/ER/60674-2; ON: DE90002037
- Country of Publication:
- United States
- Language:
- English
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Mechanisms of interaction of polycyclic aromatic diol epoxides with DNA and structures of the adducts
Base sequence effects on interactions of aromatic mutagens with DNA. Progress report, September 1, 1991--August 31, 1992
Related Subjects
BIOCHEMICAL REACTION KINETICS
MODIFICATIONS
POLYCYCLIC AROMATIC HYDROCARBONS
EVALUATION
BENZOPYRENE
CARCINOGENESIS
DNA REPLICATION
DNA SEQUENCING
GENE REGULATION
PROGRESS REPORT
STRUCTURE-ACTIVITY RELATIONSHIPS
TETRAZOLES
AROMATICS
AZOLES
CONDENSED AROMATICS
DOCUMENT TYPES
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
KINETICS
NUCLEIC ACID REPLICATION
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATHOGENESIS
REACTION KINETICS
STRUCTURAL CHEMICAL ANALYSIS
550200* - Biochemistry