Reactions of 3,4-Estrone Quinone with Mimics of Amino Acid Side Chains

Abul-Hajj, Yusuf J.; Tabakovic, Katmerka; Gleason, William B.; Ojala, William H.

doi:10.1021/tx950146p

Cited by 23 publications

(23 citation statements)

References 31 publications

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“…Several unpolar and partially resolved compounds were detected at the end of the gradient (R t 45-50 min). They corresponded to previously described covalently dimeric forms 31,32 of E-2,3-Q (not indicated by UV detection, Fig. 3a), evidenced by their respective MS-MS spectra (data not shown).…”

Section: Reaction Between E-23-q and DCsupporting

confidence: 86%

Analysis of nucleoside-estrogen adducts by LC-ESI-MS-MS†

Debrauwer¹,

Paris²,

Aerden³

et al. 1998

Analyst

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Section: Reaction Between E-23-q and DCsupporting

confidence: 86%

Analysis of nucleoside-estrogen adducts by LC-ESI-MS-MS†

Debrauwer¹,

Paris²,

Aerden³

et al. 1998

Analyst

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“…The labile estrogen quinones readily react with a variety of physiologic compounds, ranging from amino acids, such as lysine and cysteine, to the tripeptide glutathione (g-glutamyl-L-cysteinylglycine), as well as fatty acids and other lipids, and nucleic acids and DNA (17,(35)(36)(37)(38). In these reactions, the quinones form Michael addition products with nucleophilic groups, typically yielding a mixture of several stable conjugation products (39,40). In view of this reactivity, one can postulate that the substrate recognition site of CYP1B1, which is in contact with E 2 -3,4-Q or E 2 -2,3-Q, does not contain lysine or cysteine residues as these amino acids would be attacked by the quinones.…”

Section: Discussionmentioning

confidence: 99%

Cytochrome P450 1B1–Mediated Estrogen Metabolism Results in Estrogen-Deoxyribonucleoside Adduct Formation

Belous¹,

Hachey

Dawling³

et al. 2007

Cancer Research

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The oxidative metabolism of estrogens has been implicated in the development of breast cancer; yet, relatively little is known about the mechanism by which estrogens cause DNA damage and thereby initiate mammary carcinogenesis. To determine how the metabolism of the parent hormone 17B-estradiol (E 2 ) leads to the formation of DNA adducts, we used the recombinant, purified phase I enzyme, cytochrome P450 1B1 (CYP1B1), which is expressed in breast tissue, to oxidize E 2 in the presence of 2 ¶-deoxyguanosine or 2 ¶-deoxyadenosine. We used both gas and liquid chromatography with tandem mass spectrometry to measure E 2 , the 2-and 4-catechol estrogens (2-OHE 2 , 4-OHE 2 ), and the depurinating adducts 4-OHE 2 -1(A,B)-N7-guanine (4-OHE 2 -N7-Gua) and 4-OHE 2 -1(A,B)-N3-adenine (4-OHE 2 -N3-Ade). CYP1B1 oxidized E 2 to the catechol 4-OHE 2 and the labile quinone 4-hydroxyestradiol-quinone to produce 4-OHE 2 -N7-Gua and 4-OHE 2 -N3-Ade in a time-and concentration-dependent manner. Because the reactive quinones were produced as part of the CYP1B1-mediated oxidation reaction, the adduct formation followed MichaelisMenten kinetics. Under the conditions of the assay, the 4-OHE 2 -N7-Gua adduct (K m , 4.6 F 0.7 Mmol/L; k cat , 45 F

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“…Several studies (Abul-Hajj et al, 1996;Iverson et al, 1996) on the reactivity of o-quinone have demonstrated that attack of nucleophiles presented the hard and soft acid and bases (HSAB) theory (Pearson, 1973); that is, 1,4 Michael addition for oxo and amino groups and 1,6 Michael addition for thio groups. The high cytotoxic activity of DBP may be responsible for the formation of o-quinone of this compound.…”

Section: Figmentioning

confidence: 99%

Radical Production and Cytotoxic Activity oftert-Butyl-Substituted Phenols

Saito

Atsumi²,

Satoh³

et al. 2001

In Vitro & Molecular Toxicology

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2,4,6-Tri-tert-butylphenol (TBP)-related compounds are used for stabilizing plastics by making them resistant to oxidation. However, the cytotoxic activity of these compounds has not yet been established. TBP produced phenoxyl radicals at pH >or= 9.0 and 2,4-di-t-butylphenol (DBP) at pH 12.5, but 3,3',5,5'-tetra-t-butyl-1,1'-biphenyl-2,2'-diol (bisDBP) did not, using ESR spectroscopy. Both superoxide anion radical (O(2)(-)) scavenging activity and reactive oxygen species (ROS) production activity declined in the order of TBP > DBP > bisDBP. The cytotoxic activity against human oral tumor cell lines (HSC-2, HSG) and human gingival fibroblast cells (HGF) declined in the order of DBP >> bisDBP = TBP = TBP-OOH (2,4,6-tri-t-butyl-4-hydroperoxy-2,5-cyclohexadiene-1-one). The cytotoxic activity of TBP, but not of DBP or bisDBP was significantly enhanced after visible light (VL)-irradiation for 10 min. The cytotoxicity of irradiated TBP was significantly higher than that of either original TBP or TBP-OOH, the oxidative metabolite of TBP, possibly due to the formation of TBP stable radical and ROS via oxidation. In contrast, the cytotoxic activity of DBP and bisDBP was independent of radical production, and therefore, may be intrinsic. A non-enzymatic oxidation decomposition of DBP or TBP was estimated from the formation of reaction enthalpy (DeltaH) using a modified neglect of diatomic overlap, parametric method 3 (MNDO-PM3) semi-empirical method, suggesting that O(2) is capable of activating DBP to a reactive quinone or dimer and that TBP phenoxyl radicals via oxidation directly affect extra- or intracellular bioactive materials, resulting in the induction of cytotoxicity.

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Reactions of 3,4-Estrone Quinone with Mimics of Amino Acid Side Chains

Cited by 23 publications

References 31 publications

Analysis of nucleoside-estrogen adducts by LC-ESI-MS-MS†

Analysis of nucleoside-estrogen adducts by LC-ESI-MS-MS†

Cytochrome P450 1B1–Mediated Estrogen Metabolism Results in Estrogen-Deoxyribonucleoside Adduct Formation

Radical Production and Cytotoxic Activity oftert-Butyl-Substituted Phenols

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