Synthesis and identification of benzo[a]pyrene-guanine nucleoside adducts formed by electrochemical oxidation and by horseradish peroxidase catalyzed reaction of benzo[a]pyrene with DNA

Rogan, Eleanor G.; Cavalieri, Ercole L.; Tibbels, S. R.; Cremonesi, Paolo; Warner, C. D.; Nagel, Donald; Tomer, Kenneth B.; Cerny, Ronald L.; Gross, Michael L.

doi:10.1021/ja00220a049

Cited by 126 publications

(143 citation statements)

References 6 publications

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“…Unstable adduct formation has been reported to result from another route involving peroxidative activation of the parent compound DB[a,l]P to a radical cation (20). To investigate this, we first incubated purified B11 DNA in various concentrations of DB[a,l]P in the presence of HRP and hydrogen peroxide under conditions reported to activate DB[a,l]P to radical cations (28) and analyzed the DNA as before (Fig. 4).…”

Section: Experiments With Db[al]pmentioning

confidence: 99%

Formation of stable adducts and absence of depurinating DNA adducts in cells and DNA treated with the potent carcinogen dibenzo[ a,l ]pyrene or its diol epoxides

Melendez-Colon

Smith²,

Seidel³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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To measure apurinic sites they were converted to strand breaks, and these were monitored by examining the integrity of a particular restriction fragment of the dihydrofolate reductase gene. The method easily detected apurinic sites resulting from methylation by treatment of cells or DNA with dimethyl sulfate or from reaction of DNA with DB[a,l]P in the presence of horseradish peroxidase. We estimate the method could detect 0.1 apurinic site in the 14-kb fragment examined. However, apurinic sites were below our limit of detection in DNA treated directly with (؉)-syn-or (؊)-anti-DB[a,l]PDE or in DNA from Chinese hamster ovary B11 cells so treated, although in these samples the frequency of stable adducts ranged from 3 to 10 per 14 kb. We also treated the human mammary carcinoma cell line MCF-7 with DB[a,l]P and again could not detect significant amounts of unstable adducts. These results indicate that the proportion of stable adducts formed by DB[a,l]P activated in cells and its diol epoxides is greater than 99% and suggest a predominant role for stable DNA adducts in the carcinogenic activity of DB[a,l]P.

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Section: Experiments With Db[al]pmentioning

confidence: 99%

Formation of stable adducts and absence of depurinating DNA adducts in cells and DNA treated with the potent carcinogen dibenzo[ a,l ]pyrene or its diol epoxides

Melendez-Colon

Smith²,

Seidel³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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“…FAB MS and tandem mass spectrometry on an instrument of EBE geometry have been employed to characterize the dGuo adducts of BaP formed by electrochemical oxidation and those adducts formed by the in vitro reaction of BaP (not BPDE) with DNA catalyzed by HRP (140). Adducts of Gua and dGuo were formed by the binding of the BaP C-6 to either the C-8 (XXXIX) or the N-7 (XL) position of the Gua base with the former adduct predominating in both reaction systems.…”

Section: F Pah-dna Adducts Attributed To One-electron Oxidationmentioning

confidence: 99%

Mass spectrometry for the analysis of carcinogen‐DNA adducts

Chiarelli

Lay

1992

Mass Spectrometry Reviews

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“…The synthesis was performed as previously described elsewhere (Rogan et al, 1988). Briefly, 35 ml of freshly distilled dimethylformamide (DMF) containing 0.5 M of KClO 4 was placed in the electrochemical cell under argon.…”

Section: Electrochemical Synthesis Of B[a]p Adductsmentioning

confidence: 99%

“…The collision-induced dissociation mass spectra features of the different B[a]P adducts are not sufficient to attribute completely the exact chemical structure of these adducts, and more precisely the site of binding between B[a]P and dGuo. However, comparison of mass spectrometric and chromatographic features of purified adducts with published data strongly suggests that the adduct C obtained in higher yield is B[a]P-C8-dGuo, and that the two other minor stable adducts are most probably N2 and N3 dGuo adducts (Rogan et al, 1988). Prior to performing additional experiments to determine the chemical structure of the adducts, efforts were first devoted to define which one, if any, was generated in cells.…”

Section: Synthesis Of Bpde and B[a]p Dna Adductsmentioning

confidence: 99%

Influence of the metabolic properties of human cells on the kinetic of formation of the major benzo[a]pyrene DNA adducts

Marie

Maı̂tre²,

Douki

et al. 2008

J of Applied Toxicology

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Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants. Some of them, including benzo[a]pyrene (B[a]P), are tumorigenic due to their ability to generate DNA adducts. In order to define potential biomarkers of B[a]P exposure, the aim of the study was to identify the major stable DNA adducts in B[a]P-treated human cells. The role played by cellular metabolism on the nature and frequency of the DNA lesions was investigated using keratinocytes (HaCat) and actively metabolizing hepatocytes (HepG2) cell lines. Quantification of DNA damage was carried out by HPLC coupled to tandem mass spectrometry, a sensitive method making possible the selective detection of the different potential stable DNA adducts of B[a]P. These include two adducts of the 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) pathway and three adducts of the radical cation pathway. The results indicate that incubation of cells with B[a]P induces almost exclusively the formation of BPDE DNA adducts on purine bases. The amount of DNA adducts generated in hepatocytes was found to be two orders of magnitude higher than that measured in keratinocytes. Interestingly, the level of the DNA adducts produced in the cells incubated with (+/-)-anti-BPDE was similar in the two cell lines, indicating that the difference observed upon incubation with B[a]P could be attributed to different kinetics of B[a]P metabolism. The repair rate of BPDE DNA adducts was identical in the two cell lines with a half-life estimated to be around 20 h. These data support the use of the stable BPDE DNA adducts, as relevant biomarkers of exposure to B[a]P.

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Synthesis and identification of benzo[a]pyrene-guanine nucleoside adducts formed by electrochemical oxidation and by horseradish peroxidase catalyzed reaction of benzo[a]pyrene with DNA

Cited by 126 publications

References 6 publications

Formation of stable adducts and absence of depurinating DNA adducts in cells and DNA treated with the potent carcinogen dibenzo[ a,l ]pyrene or its diol epoxides

Formation of stable adducts and absence of depurinating DNA adducts in cells and DNA treated with the potent carcinogen dibenzo[ a,l ]pyrene or its diol epoxides

Mass spectrometry for the analysis of carcinogen‐DNA adducts

Influence of the metabolic properties of human cells on the kinetic of formation of the major benzo[a]pyrene DNA adducts

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