Photoemission probes of hydrocarbon-DNA interactions: a comparison of DNA influences on the reactivities of (.+-.)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, benzo[a]pyrene 4,5-oxide, and benz[a]anthracene 5,6-oxide

Urano, Shigeyuki; Price, Harry L.; Fetzer, Sharon M.; Briedis, Anita V.; Milliman, Ann; Lebreton, Pierre

doi:10.1021/ja00010a033

Cited by 14 publications

(18 citation statements)

References 2 publications

(4 reference statements)

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“…Similarly, the rate constant of B[ a ]PDE hydrolysis () was reduced 45 times in the presence of 0.1 M NaCl compared to native DNA containing no added salt . Our results on rate constants of hydrolysis in the presence of DNA are generally consistent with the pattern observed for anti -B[ a ]PDE ( , ) and anti -5-MeCDE (). However, the decreased rate constant values in denatured or Na + stabilized DNA in comparison with native DNA were not as dramatic as that observed for the anti -B[ a ]PDE or anti -5-MeCDE.…”

Section: Discussionsupporting

confidence: 89%

The Effect of Fluoro Substituents on Reactivity of 7-Methylbenz[a]anthracene Diol Epoxides

Baer‐Dubowska

Nair

Dubowski

et al. 1996

Chem. Res. Toxicol.

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The present study has examined potential mechanisms for the influence of F-substituents on the biologic activity of methylbenz[a]anthracenes. DNA adducts derived from reaction of the racemic bay-region anti-diol epoxides of 7-methylbenz[a]anthracene, and its 9- and 10- fluoro derivatives, with calf thymus DNA in vitro were partially characterized. All three hydrocarbon diol epoxides produced similar DNA adduct profiles upon reaction with calf thymus DNA in vitro that were composed of two deoxyganosine and two deoxyadenosine adducts (tentatively identified as trans addition products). The extent of covalent binding to calf thymus DNA, as estimated by 32P-postlabeling, was similar for all three diol epoxides. The reactivity of the unsubstituted and 10-F-substituted diol epoxide was further assessed by measuring overall pseudo-first-order rate constants for hydrolysis in water or 0.1 M Tris-HCl buffer, pH 7.0, and in the presence or absence of native or denatured DNA. The rate constant for hydrolysis of 7-methylbenz[a]anthracene diol epoxide in the absence of DNA was similar to that of 10-F-7-methylbenz[a]anthracene diol epoxide (t1/2 = 138 min vs 115 min in water, respectively, and 93 vs 83 min in 0.1 M Tris-HCl buffer, respectively). In addition, the presence of DNA accelerated hydrolysis rates to similar extents for both diol expoxides. The skin tumor-initiating activities of the 9- and 10-F-substituted 3,4-diols of 7-methyl-, 12-methyl-, and 7,12-dimethylbenz[a]anthracene were determined in SENCAR mice. The presence of F-substituents in the 9- or 10- position did not enhance or in some cases reduced the tumor-initiating activity of the 3,4-diols of these hydrocarbons. Collectively, these results, as well as previous results from our laboratory, suggest that the influence of a F-substituent at position 10 of the benz[a]anthracene nucleus is not due to increased or altered reactivity of the bay-region diol epoxide but rather likely on the initial formation of the 3,4-diol.

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Section: Discussionsupporting

confidence: 89%

The Effect of Fluoro Substituents on Reactivity of 7-Methylbenz[a]anthracene Diol Epoxides

Baer‐Dubowska

Nair

Dubowski

et al. 1996

Chem. Res. Toxicol.

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“…The intercalative noncovalent binding of BPDE to native double-stranded DNA is well-established ( − ); while intercalation is not feasible with single-stranded oligonucleotides, other kinds of noncovalent hydrophobic interactions between BPDE and single-stranded oligonucleotides may play an important role in determining the efficiency of covalent adduct formation in aqueous solutions. These hydrophobic interactions are most likely of the aromatic π−π stacking type ( − ).…”

Section: Introductionmentioning

confidence: 99%

Role of Hydrophobic Effects in the Reaction of a Polynuclear Aromatic Diol Epoxide with Oligodeoxynucleotides in Aqueous Solutions

Pirogov

Shafirovich

Kolbanovskiy

et al. 1998

Chem. Res. Toxicol.

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The need for large-scale direct synthesis of stereochemically defined and site-specific benzo[alpha]pyrenediol epoxide-oligodeoxyribonucleotide adducts for detailed NMR and other biochemical and physicochemical studies has necessitated a better understanding of variables that lead to an enhancement of the reaction yields. It is shown that, in aqueous solution, the formation of noncovalent hydrophobic complexes between 7r, 8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[alpha] pyrene (BPDE) and the single-stranded oligonucleotide 5'-d(CCATCGCTACC) precedes the covalent binding reaction of BPDE with the single deoxyguanosine residue. The yield of covalent reaction products (involving reaction of BPDE at the C10 position with the exocyclic amino group of the dG residue) increases with increasing DNA concentration and tends toward saturation at oligonucleotide single-strand concentrations above approximately 3 mM. The addition of NaCl (0.3 M) also tends to enhance the adduct reaction yields. However, organic solvents such as tetrahydrofuran in the reaction mixtures (10-40%) decrease the stabilities of the noncovalent complexes, which in turn leads to reductions in the yields of covalent BPDE-dG oligonucleotide adducts. The efficiencies of formation of hydrophobic complexes were probed by fluorescence and UV absorption techniques using the BPDE tetrol hydrolysis product 7,8,9,10-tetrahydroxytetrahydrobenzo[alpha]pyrene as a model system.

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“…In our rapid fluorescence displacement assay, the time to measure each PAH metabolite did not exceed five minutes. Therefore, the buffer solution was not suitable and the reaction time was not sufficient to form stable covalent adducts, although covalent adducts could form during the incubation of PAH metabolites and DNA in an aqueous solution at room temperature (Geacintov et al, 1991;Urano et al, 1991;Pirogov et al, 1998). Measurements performed under this situation were done to investigate the predominant noncovalent interaction between the metabolites and DNA.…”

Section: Binding Studies Of Pah Metabolites To P53 Cdnamentioning

confidence: 99%

Evaluation of the noncovalent binding interactions between polycyclic aromatic hydrocarbon metabolites and human p53 cDNA

Wei¹,

Lin²,

Zhang³

et al. 2010

Science of The Total Environment

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The binding of reactive polycyclic aromatic hydrocarbon (PAH) metabolites, formed enzymatically, to DNA is a crucial step in PAH carcinogenesis in vivo. We investigated the noncovalent binding interactions between 11 PAH metabolites and human p53 complementary DNA (p53 cDNA) using the fluorescence displacement method and molecular docking analysis. All of the examined metabolites predominantly interacted with p53 cDNA by intercalation instead of groove binding. The dissociation constants ranged from 0.02 to 12.34 μM. Of the metabolites tested, 1-hydroxypyrene and 3-hydroxybenzo[a]pyrene showed the strongest binding affinities to DNA, while 2-naphthol was the weakest DNA intercalator. The intercalation of the metabolites was stabilized by stacking the PAH phenyl rings with the DNA base pairs and the formation of hydrogen bonds between the oxide or hydroxyl groups on the metabolites, and DNA bases or backbones. The binding of the metabolites to DNA showed some sequence selectivity. The binding affinities and hydrogen bonds for 3-hydroxybenzo[a]pyrene, benzo[a]pyrene-4,5-dihydroepoxide (BPE) and benzo[a]pyrene-r-7,t-8-dihydrodiol-t-9,10-epoxide (BPDE) differed. It seems that the functional groups on the periphery of the PAH aromatic ring play crucial roles in regulating its binding affinity with DNA. Although it was difficult to determine the correlation between DNA noncovalent binding affinity and carcinogenicity for some of the PAH metabolites, the present study improved our understanding of the formation of PAH metabolite-DNA adducts.

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Photoemission probes of hydrocarbon-DNA interactions: a comparison of DNA influences on the reactivities of (.+-.)-trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, benzo[a]pyrene 4,5-oxide, and benz[a]anthracene 5,6-oxide

Cited by 14 publications

References 2 publications

The Effect of Fluoro Substituents on Reactivity of 7-Methylbenz[a]anthracene Diol Epoxides

The Effect of Fluoro Substituents on Reactivity of 7-Methylbenz[a]anthracene Diol Epoxides

Role of Hydrophobic Effects in the Reaction of a Polynuclear Aromatic Diol Epoxide with Oligodeoxynucleotides in Aqueous Solutions

Evaluation of the noncovalent binding interactions between polycyclic aromatic hydrocarbon metabolites and human p53 cDNA

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