Modification of deoxyribonucleic acid by a diol epoxide of benzo(a)pyrene. Relation to deoxyribonucleic acid structure and conformation and effects on transfectional activity

Journal Article · Mon Nov 12 23:00:00 EST 1979 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00590a016· OSTI ID:5450845

Pulkrabek, P; Leffler, S; Grunberger, D; Weinstein, I B

The effects of secondary structure on DNA modification by (+-)-7..beta..,9..cap alpha..-dihydroxy-9..cap alpha.., 10..cap alpha..-epoxy,7,8,9,10-tetrahydrobenzo(a)pyrene ((+-)BPDE I) were investigated. No differences in the total extent of (+-)BPDE I binding to double- and single-stranded calf thymus DNA were found. High-performance liquid chromatograhy (LC) of the nucleoside adducts obtained from hydrolysates of native and denatured calf thymus, as well as from superhelical and linear plasmid DNA, indicated that in all cases the major adduct (60 to 80% of total adducts) were formed by reaction of the (+) enantiomer of BPDE I with the N-2 position of dG residues in the DNA. A minor adduct formed from the reaction of the (-) enantiomer with dG residues was also detected and was present in greater amounts in denatured DNA than in native DNA. Small amounts of BPDE I-dA and BPDE I-dC adducts were also detected in both the single- and double-stranded DNAs. Restriction enzyme analysis of BPDE I modified SV40 and phage lambda DNA provided evidence that the modification of DNA by this carcinogen is fairly random with respect to nucleotide sequence. Partial hydrolysis of modified plasmid DNA by the single-strand-specific S/sub 1/ nuclease and LC analysis of the nucleoside adducts in the digested and undigested fractions of the DNA revealed no preferential excision by the S/sub 1/ nuclease of the different BPDE I-deoxynucleoside adducts. Functional changes in BPDE I modified DNA were demonstrated. With increasing extents of modification, there was a decrease in the ability of plasmid DNA to transfect a receptive Escherichia coli strain to antibiotic resistance.

• Research Organization: Columbia Univ., New York
• OSTI ID: 5450845
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 18:23; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550200 -- Biochemistry
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOLS
ANIMALS
AROMATICS
BENZOPYRENE
BIOLOGICAL EFFECTS
BODY
CATTLE
CELL CONSTITUENTS
CHEMICAL BONDS
CHEMICAL REACTIONS
CHROMATOGRAPHY
CONDENSED AROMATICS
COWS
DATA
DATA FORMS
DECOMPOSITION
DNA
DOMESTIC ANIMALS
ENZYMES
EPOXIDES
EXPERIMENTAL DATA
GLYCOLS
GRAPHS
HYDROCARBONS
HYDROLYSIS
HYDROXY COMPOUNDS
INFORMATION
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
LYMPHATIC SYSTEM
LYSIS
MAMMALS
MOLECULAR STRUCTURE
NUCLEASES
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PHOSPHOTRANSFERASES
PLASMIDS
RIBOSIDES
RUMINANTS
SEPARATION PROCESSES
SOLVOLYSIS
SYMMETRY
TABLES
THYMUS
TIME DEPENDENCE
TRANSCRIPTION
TRANSFERASES
TRITIUM COMPOUNDS
VERTEBRATES