An electron spin resonance study of o-semiquinones formed during the enzymatic and autoxidation of catechol estrogens.

Kalyanaraman, Balaraman; Sealy, Roger C.; Sivarajah, Kandiah

doi:10.1016/s0021-9258(18)89847-7

Cited by 68 publications

(26 citation statements)

References 26 publications

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“…In mammalian cells, CE are typically conjugated by catechol O -methyltransferases (COMT) to give their monomethoxy derivatives (Scheme ). These enzymes are protective, because only nonmethylated CE can be oxidized to their quinones (CE-Q) by peroxidases and cytochrome P450 ( 3 , − . It is hypothesized that CE-Q are the ultimate carcinogenic forms of estrogens, because these electrophiles can covalently bind to nucleophilic groups on DNA via a Michael addition.…”

Section: Introductionmentioning

confidence: 99%

Molecular Characteristics of Catechol Estrogen Quinones in Reactions with Deoxyribonucleosides

Stack

Byun

Gross

et al. 1996

Chem. Res. Toxicol.

218

281

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Estrogens can have two roles in the induction of cancer: stimulating proliferation of cells by receptor-mediated processes, and generating electrophilic species that can covalently bind to DNA. The latter role is thought to proceed through catechol estrogen metabolites, which can be oxidized to o-quinones that bind to DNA. Four estrogen-deoxyribonucleoside adducts were synthesized by reaction of estrone 3,4-quinone (E1-3,4-Q), 17 beta-estradiol 3,4-quinone (E2-3,4-Q), or estrone 2,3-quinone (E1-2,3-Q) with deoxyguanosine (dG) or deoxyadenosine (dA) in CH3CO2H/H2O (1:1). Reaction of E1-3,4-Q or E2-3,4-Q with dG produced specifically 7-[4-hydroxyestron-1(alpha, beta)-yl]guanine (4-OHE1-1(alpha, beta)-N7Gua) or 7-[4-hydroxyestradiol-1(alpha, beta)-yl]-guanine (4-OHE2-1(alpha, beta)-N7Gua), respectively, in 40% yield, with loss of deoxyribose. These two quinones did not react with dA, deoxycytidine, or thymidine. When E1-2,3-Q was reacted with dG or dA, N2-(2-hydroxyestron-6-yl)deoxyguanosine (2-OHE1-6-N2dG, 10% yield) and N6-(2-hydroxyestron-6-yl)deoxyadenosine (2-OHE1-6-N6dA, 80% yield), respectively, were formed. These adducts provide insight into the type of DNA damage that can be caused by o-quinones of the catechol estrogens. The estrogen 3,4-quinones are expected to produce depurinating guanine adducts that are lost from DNA, generating apurinic sites, whereas the 2,3-quinones would form stable adducts that remain in DNA, unless repaired. The adducts reported here will be used as references in studies to elucidate the structure of estrogen adducts in biological systems.

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Section: Introductionmentioning

confidence: 99%

Molecular Characteristics of Catechol Estrogen Quinones in Reactions with Deoxyribonucleosides

Stack

Byun

Gross

et al. 1996

Chem. Res. Toxicol.

218

281

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“…These differences may be due to the type of reaction, which is reported to be one-electron oxidation, yielding a semiquinone radical, in the case of peroxidase or K3[Fe(CN)e] oxidation (McDonald and Hamilton, 1973), and two-electron oxidation yielding the o-quinone in the case of polyphenol oxidase (Kalyanamaran et al, 1984). They may also be related to incubation conditions such as pH and ionic strength which can influence the coupling reactions between the chemical species present in solution.…”

Section: Introductionmentioning

confidence: 99%

Influence of pH on the Enzymic Oxidation of (+)-Catechin in Model Systems

Guyot¹,

Cheynier²,

Souquet³

et al. 1995

J. Agric. Food Chem.

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PPO-catalyzed oxidation of (+)-catechin was performed in aqueous buffers in the pH range 3-7, using the same level of PPO activity at all pH values. Concentration of (+)-catechin and major oxidation products was monitored by HPLC. The nature and amounts of products formed were highly pH dependent. The solutions oxidized at pH below 4 contained mostly colorless products Umax 280 nm), whereas yellow compounds (Amax 385-415 nm), eluting later than the colorless ones, predominated at higher pH values. Seven of them were purified by semipreparative HPLC. FAB-MS and acid hydrolysis data indicated they were dimers differing from natural procyanidins.

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“…With elevated rates of CE synthesis or deficient monomethylation of CE, these metabolites can be easily oxidized to semiquinones and quinones. Autoxidation of CE to semiquinones and subsequently to quinones is possible in neutral and alkaline solutions (17). Horseradish peroxidase (HRP)-catalyzed oxidation of CE forms semiquinones, which by disproportionation produce quinones and CE, while tyrosinase produces quinones, which in the 0893-228x/92/2705-0828$03.00/0 presence of CE by reverse disproportionation produce semiquinones (17).…”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of estrogen 2,3- and 3,4-quinones. Comparison of DNA adducts formed by the quinones versus horseradish peroxidase-activated catechol estrogens

Dwivedy

Devanesan

Cremonesi

et al. 1992

Chem. Res. Toxicol.

131

117

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Catechol estrogens (CE) are among the major metabolites of estrone (E1) and 17 beta-estradiol (E2). Oxidation of these metabolites to semiquinones and quinones could generate ultimate carcinogenic forms of E1 and E2. The 2,3- and 3,4-quinones of E1 and E2 were synthesized by MnO2 oxidation of the corresponding CE, following the method for synthesizing E1-3,4-quinone [Abul-Hajj (1984) J. Steroid Biochem. 21, 621-622]. Characterization of these compounds was accomplished by UV, nuclear magnetic resonance, and mass spectrometry. The relative stability of these compounds was determined in DMSO/H2O (2:1) at room temperature, and the 3,4-quinones were more stable than the 2,3-quinones. The four quinones directly reacted with calf thymus DNA to form DNA adducts analyzed by the 32P-postlabeling method. The adducts were compared to those formed when the corresponding CE were activated by horseradish peroxidase (HRP) to bind to DNA. The E1- and E2-2,3-quinones formed much higher levels of DNA adducts than the corresponding 3,4-quinones. In addition, many of the adducts (70-90%) formed by the E1- and E2-2,3-quinones appeared to be the same as those formed by activation of 2-OHE1 or 2-OHE2 by HRP to bind to DNA. Little overlap was observed between the adducts formed by E1- and E2-3,4-quinones and HRP-activated 4-OHE1 and 4-OHE2. These results suggest that semiquinones and/or quinones are ultimate reactive intermediates in the peroxidatic activation of catechol estrogens.

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An electron spin resonance study of o-semiquinones formed during the enzymatic and autoxidation of catechol estrogens.

Cited by 68 publications

References 26 publications

Molecular Characteristics of Catechol Estrogen Quinones in Reactions with Deoxyribonucleosides

Molecular Characteristics of Catechol Estrogen Quinones in Reactions with Deoxyribonucleosides

Influence of pH on the Enzymic Oxidation of (+)-Catechin in Model Systems

Synthesis and characterization of estrogen 2,3- and 3,4-quinones. Comparison of DNA adducts formed by the quinones versus horseradish peroxidase-activated catechol estrogens

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