Conformations of adducts formed between the genotoxic benzo[a]pyrene-7,8-dione and nucleosides studied by density functional theory

Lee, Hyun Mee; Chae, Youn-Hee; Kwon, Cheol; Kim, Seog K.

doi:10.1016/j.bpc.2006.07.015

Cited by 9 publications

(4 citation statements)

References 22 publications

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“…Also on the basis of DFT calculations, the group of Mavri and Bren has confirmed the S N 2 mechanism proposed for reaction of purines with epoxides [28,29]. Another studies concerning, e.g., ionic equilibriums in aqueous environment [30], optimal structures of the adducts and their biological implications [8,25] or the mutual influence of base pairing and adduct formation [31,32] have also been pursued.…”

Section: Introductionmentioning

confidence: 90%

“…The other sources are connected with various specific interactions between the reagents and/or the environment. These include the following: solvent effects [16,17], solvent-assisted reaction mechanisms [18,19], the influence of pH on ionic equilibriums [20][21][22][23][24] or specific interactions between reagents, in particular HBs and steric interactions [19,25].…”

Section: Introductionmentioning

confidence: 99%

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Nucleophilic properties of purine bases: inherent reactivity versus reaction conditions

Stachowicz‐Kuśnierz

Korchowiec

2015

Struct Chem

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In the present study, nucleophilic properties of adenine and guanine are examined by means of density functional theory. H? is used as a model electrophile. Two modes of H ? attack on the bases are considered: on the neutral molecule and on the anion. Solvent effects are modeled by means of polarizable continuum model. Regioselectivity of attack is studied by analyzing two contributions. The first one is the energetic ordering of the tautomers. The second is the relative inherent reactivity of nucleophilic sites in the bases. Atomic softnesses calculated by means of charge sensitivity analysis are employed for this purpose. The most reactive sites in various tautomers are identified on the ground of Li-Evans model. For adenine, it is demonstrated that both in basic and in neutral pH N7 atom possesses the most nucleophilic character. In polar solvents, N7 substitution is also most favored energetically. In basic pH and nonpolar solvents as well as in the gas phase, N9 substitution is slightly more probable. For guanine, a mixture of N7-and N9-substituted products can be expected in basic pH. In neutral pH, inherent reactivity and energy trends are opposite to each other; therefore, the substitution does not occur. Experimentally observed products of reactions with various electrophiles and in various conditions confirm the results obtained in this study.

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Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Nucleophilic properties of purine bases: inherent reactivity versus reaction conditions

Stachowicz‐Kuśnierz

Korchowiec

2015

Struct Chem

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“…CYP1A1 metabolizes BaP into hydrophilic compounds such as 7,8-diol-BaP [6]. However, 7,8-diol-BaP can be metabolized again by CYP1A1 to yield the highly electrophilic metabolite 7,8-diol-9,10-epoxy-BaP (BPDE) [7] that forms DNA adducts [8], thereby promoting mutagenic and carcinogenic processes [9].…”

Section: Introductionmentioning

confidence: 99%

Daytime Restricted Feeding Modifies the Temporal Expression of CYP1A1 and Attenuated Damage Induced by Benzo[a]pyrene in Rat Liver When Administered before CYP1A1 Acrophase

Ávila-Rosales

Dı́az-Muñoz

Camacho-Carranza

et al. 2021

Toxics

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The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that heterodimerizes with the AhR nuclear translocator (ARNT) to modulate CYP1A1 expression, a gene involved in the biotransformation of benzo[a]pyrene (BaP). The AhR pathway shows daily variations under the control of the circadian timing system. Daytime restricted feeding (DRF) entrains the expression of genes involved in the processing of nutrients and xenobiotics to food availability. Therefore, we evaluate if temporal AhR, ARNT, and CYP1A1 hepatic expression in rats are due to light/dark cycles or fasting/feeding cycles promoted by DRF. Our results show that AhR oscillates throughout the 24 h period in DRF and ad libitum feeding rats (ALF), showing maximum expression at the same time points. DRF modified the peak of ARNT expression at ZT5; meanwhile, ALF animals showed a peak of maximum expression at ZT17. An increased expression of CYP1A1 was linked to the meal time in both groups of animals. Although a high CYP1A1 expression has been previously associated with BaP genotoxicity, our results show that, compared with the ALF group, DRF attenuated the BaP-CYP1A1 induction potency, the liver DNA-BaP adducts, the liver concentration of unmetabolized BaP, and the blood aspartate aminotransferase and alanine aminotransferase activities when BaP is administered prior to the acrophase of CYP1A1 expression. These results demonstrate that DRF modifies the ARNT and CYP1A1 expression and protects from BaP toxicity.

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“…Most previous investigations of the effects of (+)-B a P DE-2 on DNA, both experimental6,27,28 and theoretical,29-34 have focused on the covalent adducts with DNA oligomers or single nucleotides. Of particular recent interest has been the characterization of the conformational behavior of (+)-B a P DE-2–DNA adducts.…”

Section: Introductionmentioning

confidence: 99%

Noncovalent Interactions of a Benzo[a]pyrene Diol Epoxide with DNA Base Pairs: Insight into the Formation of Adducts of (+)-BaP DE-2 with DNA

et al. 2010

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Non-covalent complexes of a tumorigenic benzo[a]pyrene diol epoxide with the guanine-cytosine and adenine-thymine base pairs have been examined computationally. (+)-BaP DE-2 forms covalent adducts with DNA via nucleophilic attack on the (+)-BaP DE-2 epoxide. Computational results predict five thermodynamically accessible complexes of AT with (+)-BaP DE-2 that are compatible with intact DNA. Among these, two are expected to lead to adenine adducts. In the lowest energy AT...(+)-BaP DE-2 complex, which has a gas-phase interaction energy of −20.9 kcal mol−1, the exocyclic NH2 of adenine is positioned for backside epoxide attack and formation of a trans adduct. The most energetically favorable complex leading to formation of a cis ring-opened adduct lies only 0.6 kcal mol−1 higher in energy. For GC...(+)-BaP DE-2, there are only two thermodynamically accessible complexes. The higher-lying complex, bound in the gas phase by 24.4 kcal mol−1 relative to separated GC and (+)-BaP DE-2, would lead to a trans ring opened N2-guanine adduct. In the global minimum energy GC...(+)-BaP DE-2 complex, bound by 27.3 kcal mol−1, the exocyclic NH2 group of cytosine is positioned for cis epoxide addition. However, adducts of (+)-BaP DE-2 with cytosine are rarely observed experimentally. The paucity of cytosine adducts, despite the predicted thermodynamic stability of this GC...(+)-BaP DE-2 complex, is attributed to the electrostatic destabilization of the benzylic cation intermediate thought to precede cis addition.

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Conformations of adducts formed between the genotoxic benzo[a]pyrene-7,8-dione and nucleosides studied by density functional theory

Cited by 9 publications

References 22 publications

Nucleophilic properties of purine bases: inherent reactivity versus reaction conditions

Nucleophilic properties of purine bases: inherent reactivity versus reaction conditions

Daytime Restricted Feeding Modifies the Temporal Expression of CYP1A1 and Attenuated Damage Induced by Benzo[a]pyrene in Rat Liver When Administered before CYP1A1 Acrophase

Noncovalent Interactions of a Benzo[a]pyrene Diol Epoxide with DNA Base Pairs: Insight into the Formation of Adducts of (+)-BaP DE-2 with DNA

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