Interaction of (+-)benzo(a)pyrene-7. beta. ,8. cap alpha. -diol-9. cap alpha. ,10. cap alpha. -epoxide with fractionated eukaryotic DNA

Conference · Sun Jan 01 00:00:00 EST 1978

OSTI ID:6369015

Iyer, R; Triplett, L L; Slaga, T J; Papaconstantinou, J

Chemically unreactive polycyclic aromatic hydrocarbons (PAH) exert their carcinogenic and mutagenic effects only after they are metabolized to chemically reactive species. These reactive metabolites can undergo covalent interactions with cellular RNA, DNA, and protein as well as with synthetic copolymers of nucleic acids and proteins. Studies of the binding of metabolites of benzo(a)pyrene to DNA have provided evidence that benzo(a)pyrene-7,8-diol-9,10-epoxide is responsible for most of the bound adducts, and that this interaction is primarily with the guanine residues (90%) and secondarily to adenine residues (2 to 5%). The significance of the interaction of benzo(a)pyrene-diol-epoxide with guanine, to the mechanism of chemical carcinogenesis, is not understood. In view of the apparent importance of this carcinogen-DNA interaction, we were interested in determining several parameters of this reaction that might contribute to an understanding of the mechanism of chemical carcinogenesis. Since the carcinogen is known to react with the guanine residues in DNA, one of our major aims was to determine if there are any hot spots in eukaryotic DNA where the diol-epoxide shows a preferential binding. It is well known that the eukaryotic genome is quite complex and consists of localized regions of (G+C)-rich and (A+T)-rich DNA sequences. These specific DNA sequences will enable detailed studies of the role of (G+C)-content as well as sequence specificity in the interaction of carcinogens with DNA. Our ability to carry out the present studies on the interaction of carcinogens with various fractions of mouse and calf DNA was facilitated by the recent development of techniques in our laboratory for the enrichment of (G+C)-rich and (A+T)-rich DNA sequences. A preliminary report is herewith presented on the interaction of benzo(a)pyrene-diol-epoxide with fractionated mouse and calf DNA.

• Research Organization: Tennessee Univ., Oak Ridge (USA). School of Biomedical Sciences; Oak Ridge National Lab., TN (USA)
• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 6369015
• Report Number(s): CONF-781039-3
• Resource Relation: Conference: 3. symposium on polynuclear aromatic hydrocarbons, Columbus, OH, USA, Oct 1978
• 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.
BENZOPYRENE
CONFIGURATION INTERACTION
DNA
BIOLOGICAL EFFECTS
CALVES
CARBON 14 COMPOUNDS
CARCINOGENS
CHEMICAL BONDS
EPOXIDES
IN VITRO
METABOLITES
MICE
TRACER TECHNIQUES
ANIMALS
AROMATICS
CATTLE
CONDENSED AROMATICS
DOMESTIC ANIMALS
HYDROCARBONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
RODENTS
RUMINANTS
VERTEBRATES
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