DNA alkylation and unwinding induced by benzo(a)pyrene diol epoxide: modulation by ionic strength and superhelicity

Journal Article · Tue Apr 01 00:00:00 EST 1980 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.77.4.2000· OSTI ID:5059541

Gamper, H B; Straub, K; Calvin, M; Bartholomew, J C

Superhelical and partially relaxed DNAs of simian virus 40 were allowed to react in vitro with(+-)-7..beta..,8..cap alpha..-dihydroxy-9..cap alpha..,10..cap alpha..-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BaP diol epoxide). The modified DNA contained N/sup 2/ guanine and N/sup 6/ adenine hydrocarbon adducts in the ratio 86:14. Superhelical simian virus 40 DNA was approximately 6% more susceptible to modification than was partially relaxed viral DNA. Counterions inhibited DNA alkylation by up to 80%, Mg/sup 2 +/ being 50-fold more effective than Na/sup +/. The sensitivity of covalent binding to helix stability is consistent with a reaction complex in which BaP diol epoxide is intercalated. The superhelical density of the modified DNA substrates was determined electrophoretically relative to partially relaxed standards, and an unwinding angle for the hydrocarbon adducts was calculated. The angle was dependent upon the superhelicity of the DNA molecule and ranged from 330/sup 0/ to 30/sup 0/. These data indicate that the modified base pairs are disrupted and, in the presence of torsional strain, act as centers for the further denaturation of up to eight adjacent base pairs. In the absence of such strain the alkylation sites have an ordered structure, with the attached hydrocarbon probably oriented in the minor or major groove of the helix.

• Research Organization: Univ. of California, Berkeley
• DOE Contract Number: W-7405-ENG-48
• OSTI ID: 5059541
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 77:4; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
ALKYLATION
AROMATICS
BENZOPYRENE
BIOCHEMICAL REACTION KINETICS
CHEMICAL REACTIONS
CHROMATOGRAPHY
CONDENSED AROMATICS
CONFIGURATION
DNA
ELECTROPHORESIS
EPOXIDES
GLYCOLS
HELICAL CONFIGURATION
HYDROCARBONS
HYDROXY COMPOUNDS
IONIC COMPOSITION
KINETICS
LIQUID COLUMN CHROMATOGRAPHY
METABOLITES
MICROORGANISMS
MOLECULAR STRUCTURE
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PARASITES
REACTION KINETICS
SEPARATION PROCESSES
SIMIAN VIRUS
TOXICITY
VIRUSES