Base sequence effects on interactions of aromatic mutagens with DNA

Technical Report · Thu Sep 19 00:00:00 EDT 1991

DOI:https://doi.org/10.2172/5047004· OSTI ID:5047004

Geacintov, N E

Within this period, we have completed our investigations on the thermodynamic characteristics and base sequence dependence of duplex formation of benzo(a)pyrene diol epoxide (BPDE) DNA adducts. Different 11-mer oligonucleotides containing covalently bound BPDE moieties at the exocyclic amino group of a single guanine base were utilized in these studies. Last year, in the three-year progress report, some preliminary data were discussed. A final account is provided here. New techniques were developed for assessing the preferred orientations of the enantiomers of (+)-BPDE and ({minus})-BPDE relative to the 5in {r arrow} 3in polarity of DNA strands; these investigations were prompted by predictions derived from our computer modeling studies. Significant progress was made towards synthesizing BPDE-adenine adducts in base sequence-specific oligonucleotides. We failed, on the other hand, to synthesize nitrosopyrene-oligonucleotide adducts because of intrinsic low reactivities of the nitrenium derivative ions with oligonucleotides. Nature was against us in this effort. Therefore, this particular goal to be abandoned. 14 refs., 8 figs., 4 tabs.

• Research Organization: New York Univ., NY (United States)
• Sponsoring Organization: USDOE; USDOE, Washington, DC (United States)
• DOE Contract Number: FG02-88ER60674
• OSTI ID: 5047004
• Report Number(s): DOE/ER/60674-4; ON: DE92002476
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
DNA ADDUCTS
COMPUTERIZED SIMULATION
MOLECULAR STRUCTURE
POLYCYCLIC AROMATIC HYDROCARBONS
BIOLOGICAL EFFECTS
METABOLITES
ABSORPTION SPECTROSCOPY
ADENINES
BENZOPYRENE
BIOCHEMICAL REACTION KINETICS
DNA
DNA MISMATCH
EPOXIDES
GUANINE
MUTAGENS
NUCLEIC ACID DENATURATION
OLIGONUCLEOTIDES
PROGRESS REPORT
STEREOCHEMISTRY
THERMODYNAMIC PROPERTIES
TOXICITY
ADDUCTS
AMINES
ANTIMETABOLITES
AROMATICS
AZAARENES
CONDENSED AROMATICS
DOCUMENT TYPES
DRUGS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYDROXY COMPOUNDS
KINETICS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PHYSICAL PROPERTIES
PURINES
REACTION KINETICS
SIMULATION
SPECTROSCOPY
550200* - Biochemistry
550400 - Genetics
560300 - Chemicals Metabolism & Toxicology