Detection of polycyclic aromatic hydrocarbon-DNA adducts in human lung. 1993

A Weston, and E D Bowman, and P G Shields, and G E Trivers, and M C Poirier, and R M Santella, and D K Manchester
Laboratory of Human Carcinogenesis, National Cancer Institute, Bethesda, MD 20892.

Synchronous fluorescence spectroscopy has been combined with immunoaffinity chromatography (IAC) and HPLC to detect polycyclic aromatic hydrocarbon (PAH)-DNA adducts and measure r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE)-DNA adducts in human tissues and cells. A monoclonal antibody (8E11) that recognizes a range of PAH-DNA adducts, but not chemically unrelated adducts, was used to prepare IAC columns. Samples of DNA (25 from human lung and 8 positive and negative controls) were hydrolyzed enzymically and subjected to IAC. Adducts captured by the antibodies and eluted in NaOH (50 mM) were analyzed for fluorescent properties. The spectral fluorescence excitation-emission matrices suggested the presence of mixtures of PAH-DNA adducts in some of the eluates. The eluates were subsequently hydrolyzed with acid (HCl, 0.1 N, 3 hr) and reanalyzed by synchronous fluorescence spectroscopy using a wavelength differential of 34 nm. In 6 of the 25 human lung DNA samples, materials with HPLC retention times identical to benzo[a]pyrene-7,10/8,9-tetrahydrotetrol were found to have fluorescence characteristics indistinguishable from pyrene. Comparisons with appropriate standards indicated that BPDE-DNA adduct levels were between 1 and 40 adducts in 10(8) unmodified nucleotides. No correlation was observed between lung DNA-adduct levels and measures of recent smoking (serum cotinine), but tissue samples taken from different portions of the same lungs showed variation in the DNA adduct levels detected. This finding complicates interpretation of the data and has important implications for the design of future experiments.

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011083 Polycyclic Compounds Compounds which contain two or more rings in their structure. Compounds, Polycyclic
D002846 Chromatography, Affinity A chromatographic technique that utilizes the ability of biological molecules, often ANTIBODIES, to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Chromatography, Bioaffinity,Immunochromatography,Affinity Chromatography,Bioaffinity Chromatography
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

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