Base sequence selectivity in the binding of 7(R),8(S)-dihydroxy-9(S),10(R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene to oligodeoxyribonucleotide duplexes
- Purdue Univ., West Lafayette, IN (United States)
Benzo[a]pyrene (B[a]P) is a widespread environmental pollutant which arises from the combustion of fossil fuels in heat and power generation and refuse burning, as well as from vehicle emissions. B[a]P can be metabolized by eukaryotic cells to ultimate carcinogenic metabolites (benzo[a]pyrene diol epoxides) which bind to DNA. The effect of nucleotide sequence on the binding of 7(R),8(S)-dihydroxy-9(S), 10(R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE] to the exocyclic amino group of deoxyguanosine was investigated in duplexes formed by self-complementary oligodeoxyribonucleotide decamers which contained two deoxyguanosines (dGs) within unique sequences. A [sup 35]S-postlabeling procedure was developed for analysis of (+)-anti-BPDE adducts as dinucleotides containing 5'-(+)-anti-BPDE-dG adducts. This allows identification of the 3' neighbor of the reacted guanine and permits quantitation of the binding of (+)-anti-BPDE to each specific guanine in the oligodeoxyribonucleotide duplexes. Of all the central dG-containing sequences studied, dG surrounding by deoxycytidines (CGC) reacted to the greatest extent: over 4-fold more (+)-anti-BPDE bound to this central dG compared to the least reactive deoxyguanosine (AGT). (+)-anti-BPDE exhibited a preference for binding to a central deoxyguanosine when either the 5' or 3' neighbor was deoxyguanosine. The binding of (+)-anti-BPDE to oligeodeoxyribonucleotide duplexes containing different numbers of consecutive dGs was analyzed in order to determine how the length of these sequences influences binding. Increases in the length of consecutive deoxyguanoisine residues from 3 to 5 had little effect on the quantity of (+)-anti-BPDE bound to dG above that expected from the presence of a neighboring dG and an increase in the number of dG residues available for reaction.
- OSTI ID:
- 6906351
- Journal Information:
- Chemical Research in Toxicology; (United States), Journal Name: Chemical Research in Toxicology; (United States) Vol. 7:1; ISSN CRTOEC; ISSN 0893-228X
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
AMINES
AROMATICS
AZAARENES
BENZOPYRENE
BIOCHEMICAL REACTION KINETICS
CHEMICAL BONDS
CONDENSED AROMATICS
DNA ADDUCTS
DNA SEQUENCING
EPOXIDES
GUANINE
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYDROXY COMPOUNDS
KINETICS
MUTAGENESIS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PURINES
REACTION KINETICS
STRUCTURAL CHEMICAL ANALYSIS
STRUCTURE-ACTIVITY RELATIONSHIPS