Base sequence effects on interactions of aromatic mutagens with DNA
This work is concerned with polycyclic aromatic hydrocarbons (PAH), which are known to be carcinogenic in mammals and are mutagenic in prokaryotic test systems. The PAH compounds are by-products of combustion of fossil fuels and are emitted into the environment. In vivo, they are activated metabolically to reactive epoxide intermediates which bind noncovalently and covalently to DNA. The formation of DNA adducts gives rise to mutations, and is believed to be the key initial event in the complex, multi-stage tumorigenesis process. The General Objectives of this project were:the development of techniques for a through understanding of the mechanisms of action of mutagenic and tumorigenic PAH epoxide metabolites; differentiate the mechanisms by which these biologically active compounds and their inactive isomers damage DNA, and the differences in the biological end-points produced; develop new and sensitive techniques for monitoring the presence of biologically deleterious and benign PAH-DNA lesions in cellular DNA. This quarter, the characteristics and base sequence-dependence of the binding of the tumorigenic (+)-anti-benzo (a) pyrene-7,8-diol-9,10-oxide (BPDE) and the non-tumorigenic ({minus})-isomer to nucleic acids have been determined. The sequence- and isomer-dependent covalent binding by cis and trans addition to the exocyclic amino-group of guanine has been established in synthetic polynucleotides and oligonucleotides of defined base composition and sequence. 50 refs., 19 figs.
- Research Organization:
- New York Univ. (NYU), NY (United States)
- Sponsoring Organization:
- DOE/ER
- DOE Contract Number:
- FG02-88ER60674
- OSTI ID:
- 6368272
- Report Number(s):
- DOE/ER/60674-3; ON: DE91004591
- Country of Publication:
- United States
- Language:
- English
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Base sequence effects on interactions of aromatic mutagens with DNA
Base sequence effects on interactions of aromatic mutagens with DNA (deoxyribonucleic acid)
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
20 FOSSIL-FUELED POWER PLANTS
DNA
CHEMICAL BONDS
DNA ADDUCTS
BIOLOGICAL EFFECTS
METABOLITES
NUCLEIC ACIDS
POLYCYCLIC AROMATIC HYDROCARBONS
BIOCHEMICAL REACTION KINETICS
COMBUSTION PRODUCTS
EPOXIDES
FOSSIL FUELS
GUANINE
MUTAGENS
NEOPLASMS
POLLUTANTS
PROGRESS REPORT
SPECTRA
STEREOCHEMISTRY
THERMODYNAMICS
ADDUCTS
AMINES
AROMATICS
AZAARENES
DISEASES
DOCUMENT TYPES
ENERGY SOURCES
FUELS
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
HYDROXY COMPOUNDS
KINETICS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PURINES
REACTION KINETICS
550200* - Biochemistry
560300 - Chemicals Metabolism & Toxicology
200400 - Fossil-Fueled Power Plants- Health & Safety- (1990-)