COMTOxygen speciesXenobiotic metabolismMetabolismIntermediatesReceptorCysteineReceptorsProteinsFunctionalPotentMolecularNaturalActivityEffectsMetabolitesProduction of reactive oxygenEstradiolSpeciesEndogenous estrogensOxygenQuinonesOxidativePathwaysCYP1B1BioactivationESR1MoleculesMetabolicConcentrationsDamageCholesterolShownHighlyFreeRiskEffectsSimilarTotalLackRole
COMT4
- The present case-control study aimed to investigate the main effect of polymorphisms in genes involved in xenobiotic metabolism and estrogen biosynthesis, CYP1A1, CYP1B1, COMT and CYP17, CYP19 and the BRCA1 founder mutation in relation to BC risk and to explore possible interactions between the gene polymorphisms and serum POP levels on BC risk in Greenlandic Inuit women. (biomedcentral.com)
- cytochrome P450 (CYP) 1A1, CYP1B1, Catechol-O-methyltransferase (COMT), 17α-hydroxylase and 17, 20-lyase (CYP17) and aromatase (CYP19). (biomedcentral.com)
- The expression of estrogen receptors, estrogen metabolism associated phase I genes (CYP 1A1, 1A2, 3A4, and 1B1) and phase II gene catechol-O-methyltransferase (COMT), as well as antioxidant MnSOD, were analyzed either at the RNA level by quantitative reverse transcriptase-polymerase chain reaction or at the protein level by western blot. (bvsalud.org)
- RESULTS: Expression of MnSOD and phase I genes that convert E2 into genotoxic metabolites 2-OH-E2 and 4-OH-E2 were significantly increased, whereas the expression of phase II gene COMT that detoxifies estrogen metabolites was significantly decreased in arsenic and estrogen coexposed cells. (bvsalud.org)
Oxygen species5
- These spermatozoa also experienced increased mitochondrial generation of reactive oxygen species after 1 week of exposure, with elevated DNA oxidation and fragmentation across all exposure periods. (nature.com)
- The cell viability, reactive oxygen species (ROS) levels, ratios of oxidized nicotinamide adenine dinucleotide to its reduced form (NAD + /NADH), apoptosis assays, and cellular uptake of E/PCF-NPs were determined on 4T1 cells. (dovepress.com)
- breast cancer is thought to be related to the increased production of reactive oxygen species, indicating the involvement of GPxs in these processes. (biomedcentral.com)
- It is likely to act as a bioactive compound by exerting reactive oxygen species (ROS)-scavenging activity and/or binding to specific proteins such as oxidative enzymes and transcriptional factors in signal transduction pathways. (rsc.org)
- This polyphenolic compound is known to be a strong anti-oxidant which scavenges reactive oxygen species (ROS) directly or effectively inhibits ROS-generating enzymes ( e.g. xanthine oxidase, lipoxygenase). (rsc.org)
Xenobiotic metabolism2
- Polymorphisms including single nucleotide polymorphisms (SNPs) in genes involved in xenobiotic metabolism and in genes involved in oestrogen biosynthesis and metabolism might affect circulating estrogen levels and modulate the individual susceptibility to environmental carcinogens in relation to developing BC [ 5 ]. (biomedcentral.com)
- however, differences in the distribution of polymorphisms in key candidate genes involved in estrogen/xenobiotic metabolism might contribute to variation in breast cancer susceptibility in different populations. (biomedcentral.com)
Metabolism5
- Simplified schematic presentation of enzymes involved in estrogen biosynthesis and metabolism. (biomedcentral.com)
- Cytochrome P450 1B1 (CYP1B1) is active in the metabolism of estrogens to reactive catechols and of different procarcinogens. (biomedcentral.com)
- Both estrogen and arsenic are known prostate carcinogens, however, the effect of coexposure to these two chemicals on genes involved in estrogen metabolism is not known. (bvsalud.org)
- Therefore, the objective of this study was to evaluate the role of arsenic and estrogen coexposure on the expression of estrogen receptors and estrogen metabolism-associated genes. (bvsalud.org)
- CONCLUSIONS: These novel findings suggest that coexposure to arsenic and estrogen acts synergistically in the activation of not only the estrogen receptors but also the genes associated with genotoxic estrogen metabolism and epigenetic inactivation of DNA glycosylase MBD4. (bvsalud.org)
Intermediates1
- Whereas there remains much to learn about the potential biological relevance of UGTs, deficient glucuronidation can result in either elevated tissue concentrations and direct toxicity of substrates, as with the endobiotic bilirubin, or, alternatively, enhanced bioactivation of substrates to toxic reactive intermediates, as in the case of acetaminophen and benzo[ a ]pyrene. (aspetjournals.org)
Receptor4
- To test this hypothesis, we used real-time quantitative RT-PCR to quantify the mRNA expression of a large panel of genes coding for the major xenobiotic-metabolizing enzymes (12 phase I enzymes, 12 phase II enzymes and three members of the ABC transporter family) in a small series of normal breast (and liver) tissues, and in estrogen receptor alpha (ERα)-negative and ERα-positive breast tumors. (biomedcentral.com)
- Breast cancer growth is regulated by estrogen, which acts by binding to its estrogen receptor alpha (ERα). (biomedcentral.com)
- In addition to receptor-mediated pathways, DNA-reactive estrogen metabolites have also been shown to play a critical role in mutagenicity and carcinogenicity. (bvsalud.org)
- Two types of estrogen receptor exist: ER, which is a member of the nuclear hormone family of intracellular receptors, and the estrogen G protein-coupled receptor GPR30 , which is a G protein-coupled. (absoluteastronomy.com)
Cysteine2
- Cysteine engineered anti-MUC16 antibodies are engineered by replacing one or more amino acids of a parent anti-MUC16 antibody with non cross-linked, reactive cysteine amino acids. (justia.com)
- The invention relates generally to antibodies engineered with reactive cysteine residues and more specifically to antibodies with therapeutic or diagnostic applications. (justia.com)
Receptors1
- Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens. (absoluteastronomy.com)
Proteins1
- One of the most reactive proteins was a putative surface area antigen encoded by MAP1087. (irjs.info)
Functional1
- The second major area of my group's research has involved studies into the use of structurally 'unusual' heterocycles as protected, reactive functional groups in organic synthesis. (exeter.ac.uk)
Potent1
- 4-methylcatechol is a specific, bioavailable and well-researched form of catechol that provides some potent physiological effects. (dpsnutrition.net)
Molecular1
- Together, these genetic and epigenetic aberrations provide the molecular basis for the potentiation of carcinogenicity of arsenic and estrogen coexposure in prostate epithelial cells. (bvsalud.org)
Natural1
- Catechol is a natural compound found in various fruits and vegetables. (dpsnutrition.net)
Activity1
- Earlier, we also reported the synergistic effect of arsenic and estrogen on decreased expression of MBD4 genes that play an important role in DNA repair through its DNA glycosylase activity. (bvsalud.org)
Effects2
- BACKGROUND: Previously we reported that arsenic and estrogen cause synergistic effects in the neoplastic transformation of human prostate epithelial cells. (bvsalud.org)
- Coexposure to arsenic and estrogen has synergistic effects on the expression of these genes as well as in MBD4 promoter hypermethylation. (bvsalud.org)
Metabolites11
- Catechol metabolites of endogenous estrogens induce redox cycling and generate reactive oxygen species in breast epithelial cells. (nih.gov)
- These metabolites are mutagenic and may contribute to the carcinogenic activity of estrogens. (nih.gov)
- In the present studies, we determined whether the catechol metabolites of endogenous estrogens, including 2-hydroxyestradiol, 4-hydroxyestradiol, 4-hydroxyestrone and 2-hydroxyestriol, can redox cycle in breast epithelial cells. (nih.gov)
- Using extracellular microsensors, catechol estrogen metabolites stimulated the release of H(2)O(2) by adherent cells, indicating that redox cycling occurs in viable intact cells. (nih.gov)
- [ 1-10 ] The challenges of confirming this hypothesis have been: 1) the lack of highly sensitive and reliable assays to accurately measure estrogen and its oxidative metabolites (EM) and 2) the lack of biomarkers that accurately capture environmental agents that may modify endogenous estrogens and their metabolism, making it difficult to partition out variance accounted for by the environment vs ethnicity. (medscape.com)
- Moore and colleagues [ 11 ] provide novel information on the contribution of the parent estrogens (estradiol and estrone) and their metabolites (EM) to breast cancer risk in postmenopausal Chinese women and evidence that measuring these markers could improve risk prediction in this population. (medscape.com)
- In addition to receptor-mediated pathways, DNA-reactive estrogen metabolites have also been shown to play a critical role in mutagenicity and carcinogenicity. (bvsalud.org)
- RESULTS: Expression of MnSOD and phase I genes that convert E2 into genotoxic metabolites 2-OH-E2 and 4-OH-E2 were significantly increased, whereas the expression of phase II gene COMT that detoxifies estrogen metabolites was significantly decreased in arsenic and estrogen coexposed cells. (bvsalud.org)
- 15. Bioactivation of estrone and its catechol metabolites to quinoid-glutathione conjugates in rat liver microsomes. (nih.gov)
- Sequencing of the tumor DNA as well as further mechanistic studies provided evidence that PAHs initiate carcinogenesis by inducing mutations primarily in the Ha-Ras oncogene and that this process requires a metabolic conversion of the per se non-toxic chemicals to highly reactive metabolites, a process which is primarily carried out by AHR-regulated cytochrome P450 (CYP) monooxygenases ( 10 - 12 ). (frontiersin.org)
- The 4-OH pathway is considered the most genotoxic as its metabolites can create reactive products that damage DNA. (healthmatters.io)
Production of reactive oxygen1
- These agents can induce excess production of reactive oxygen species such as superoxide, hydroxyl radicals, perioxynitrite, etc which cause the oxidation and thus damage of the mitochondria which in effect reduces their ability to produce energy. (custommedicine.com.au)
Estradiol4
- These catechol estrogens, but not estradiol, estrone, estriol or 2-methoxyestradiol, were found to redox cycle and generate hydrogen peroxide (H(2)O(2)) and hydroxyl radicals in lysates of three different breast epithelial cell lines: MCF-7, MDA-MB-231 and MCF-10A. (nih.gov)
- 8. Selective estrogen receptor modulator (SERM) lasofoxifene forms reactive quinones similar to estradiol. (nih.gov)
- 4-Methoxyestradiol (4-ME2) is an endogenous, naturally occurring methoxylated catechol estrogen and metabolite of estradiol that is formed by catechol O-methyltransferase via the intermediate 4-hydroxyestradiol. (healthmatters.io)
- Swabe G, Matthews K, Brooks M, Janssen I, Wang N, El Khoudary SR. Response to a letter to the editor on "HDL-C and arterial calcification in midlife women: The contribution of estradiol and C-reactive protein? (rush.edu)
Species5
- Redox cycling of the SQs and subsequent generation of reactive oxygen species (ROS) is also an important mechanism leading to DNA damage. (nih.gov)
- Reactive Oxygen Species (ROS) including superoxide radicals, hydroxyl radicals, singlet oxygen and hydrogen peroxide are often generated as byproducts of biological reactions or from exogenous factors ( Cerutti, 1991 ). (scialert.net)
- Extensive research has found strongly increased generation of reactive oxygen species, free radicals, and reactive nitrogen species during acute physical exercise that can lead to oxidative stress (OS) and impair muscle function. (biomedcentral.com)
- The intake of antioxidants is essential in order to prevent oxidative damage to the mitochondria caused by reactive oxygen species. (custommedicine.com.au)
- in the cell vary widely, and include ATP synthesis, metabolic integration, reactive oxygen species synthesis, and the regulation of apoptosis1. (irjs.info)
Endogenous estrogens2
- The SQs of exogenous estrogens have been shown to redox cycle, however, redox cycling and the generation of ROS by endogenous estrogens has never been characterized. (nih.gov)
- For over 45 years, scientists have hypothesized that variation in endogenous estrogens may explain ethnic differences in breast cancer incidence (ie, Asians compared with US whites). (medscape.com)
Oxygen1
- The current understanding of the molecular etiology of breast cancer hypothesizes biotransformation of E2 and E1 within the breast tissue to catechols and subsequent oxidation to genotoxic quinones resulting in DNA damage via formation of estrogen-DNA adducts or via formation of reactive oxygen species resulting in oxidative stress (Yager 2015 ). (springer.com)
Quinones2
Oxidative3
- Influence of intramammary estrogen levels and BCRF on estrogen receptor (ESR) activation, ESR-related proliferation (indicated by levels of marker transcripts), oxidative stress (indicated by levels of GCLC transcript and oxidative derivatives of cholesterol), and levels of transcripts encoding enzymes involved in estrogen biotransformation was identified by multiple linear regression models. (springer.com)
- 4. Chemical modification modulates estrogenic activity, oxidative reactivity, and metabolic stability in 4'F-DMA, a new benzothiophene selective estrogen receptor modulator. (nih.gov)
- Menopause represents a state of growing estrogen deficiency, and this loss of estrogen in the setting of physiologic aging increases the likelihood of mitochondrial dysfunction, cellular senescence, declining immune responses to injury, and disarray in the balance between antioxidant formation and oxidative stress. (wjgnet.com)
Pathways6
- The associations between concentrations of parent estrogens, individual EM, the ratio of the 2-, 4-, and 16-EM pathways to total estrogens/EM, and the ratio of one pathway to another were examined with respect to breast cancer risk. (medscape.com)
- [ 13-15 ] In multivariable analyses, there were statistically significant trends between higher quartiles of the parent estrogens, the 2-, 4-, and 16-EM pathways, and breast cancer risk. (medscape.com)
- Adjustment by the parent estrogens attenuated the point estimates of the 2-EM and 4-EM pathways to a greater degree than the 16-EM pathway, supporting the notion that there are differences in the contribution of these pathways to breast carcinogenesis. (medscape.com)
- While the parent estrogens and EM pathways have been shown to be either associated with increased risk or a reduction in risk for breast cancer, the extent to which changes in these EM pathways, impact breast carcinogenesis still needs to be understood. (medscape.com)
- The mean concentrations of EMs in the 2-, 4-, and 16-EM pathways were also increased in Asian American women compared with Chinese women, and the ratio of the 2-EM pathway to the total estrogen/EM was 35% lower in Asian Americans (higher ratios are associated with reduced breast cancer risk) while the mean concentration of the 16-EM pathway was 42% higher. (medscape.com)
- Most consider 2-OH-E1 favorable Estrogen is metabolized (primarily by the liver) down three phase I pathways. (healthmatters.io)
CYP1B11
- Furthermore, BMI was the only BCRF to indeed influence fluxes to E-DNA (via congruent adverse influence on levels of estrogens, CYP1B1 and SULT1A2 ). (springer.com)
Bioactivation3
- Whereas there remains much to learn about the potential biological relevance of UGTs, deficient glucuronidation can result in either elevated tissue concentrations and direct toxicity of substrates, as with the endobiotic bilirubin, or, alternatively, enhanced bioactivation of substrates to toxic reactive intermediates, as in the case of acetaminophen and benzo[ a ]pyrene. (aspetjournals.org)
- 1. Bioactivation of the selective estrogen receptor modulator desmethylated arzoxifene to quinoids: 4'-fluoro substitution prevents quinoid formation. (nih.gov)
- 3. Bioactivation of the selective estrogen receptor modulator acolbifene to quinone methides. (nih.gov)
ESR12
- In addition, estrogen receptor alpha (ESR1)-mediated stimulation of proliferation of the epithelial cells contributes to conversion of DNA damage into mutations (i.e., tumor initiation) as well as tumor promotion and progression (Yager 2015 ). (springer.com)
- 2007 ). Thus, tumor formation (Yager 2015 ) seems to depend on intramammary levels of both reactive estrogen biotransformation products and free estrogens able to activate ESR1 (Fig. 1 ). (springer.com)
Molecules2
- They are highly reactive with other molecules and can damage DNA, proteins and cellular membranes. (greenapplenutrition.co.uk)
- Catecholamines are molecules that have a catechol nucleus consisting of benzene with two hydroxyl side groups and a side-chain amine. (absoluteastronomy.com)
Metabolic1
- Metabolic fluxes to adducts of estrogens with DNA (E-DNA) were assessed by a metabolic network model (MNM) which was validated by comparison of calculated fluxes with data on methoxylated and glucuronidated estrogens determined by GC- and UHPLC-MS/MS. Intratissue estrogen levels significantly influenced ESR activation and fluxes to E-DNA within the MNM. (springer.com)
Concentrations3
- In The second part of the study Moore and colleagues [ 11 , 16 ] provide evidence that there are statistically significant differences not only in parent estrogen concentrations between Chinese women in China and Asian American populations but in some of the EM levels that may explain variations in breast cancer risk among women of the same ethnicity living in high- vs low-risk countries. (medscape.com)
- In their study, Asian Americans had statistically significant higher mean concentrations of parent estrogens than Chinese women in China. (medscape.com)
- The observation that Chinese women living in China had lower concentrations of parent estrogens and EM but similar associations of breast cancer risk as US women, when the highest quartile of EM is compared with the lowest quartile based on the distribution in the control female group, suggests that these two populations may differ in their sensitivity to estrogen. (medscape.com)
Damage2
- Breast cancer etiology is associated with both proliferation and DNA damage induced by estrogens. (springer.com)
- Thus, the aim of the present study was to investigate the influence of BCRF on estrogen-induced proliferation and DNA damage in 41 well-characterized breast glandular tissues derived from women without breast cancer. (springer.com)
Cholesterol1
- These are lipids that have a characteristic four-ringed structure and include hormones such as testosterone and estrogen, and cholesterol. (etutorworld.com)
Shown1
- Breast cancer risk factors (BCRF) such as body mass index (BMI), smoking, and intake of estrogen-active drugs were recently shown to influence intratissue estrogen levels. (springer.com)
Highly2
- The researchers used an analytically validated, highly accurate and reproducible liquid chromatography-tandem mass spectrometry assay [ 12 ] with internal standards to prospectively examine, in a nested case-control study with carefully matched control subjects controls, the association between urinary estrogens and breast cancer risk in a Chinese cohort of postmenopausal women. (medscape.com)
- Upon light activation, the azide moiety converts to a highly reactive nitrene that, notably, inserts into CH and NH bonds, creating highly robust covalent linkages. (monossabios.com)
Free1
- Anti oxidants are free radical scavengers that interact with the free radical to ensure it is no longer a reactive molecule. (greenapplenutrition.co.uk)
Risk1
- The ratio of the 2-EM pathway to the total estrogen/EM was associated with a large (43%) reduction in breast cancer risk when comparing the fourth quartile with the first quartile. (medscape.com)
Effects2
- BACKGROUND: Previously we reported that arsenic and estrogen cause synergistic effects in the neoplastic transformation of human prostate epithelial cells. (bvsalud.org)
- Coexposure to arsenic and estrogen has synergistic effects on the expression of these genes as well as in MBD4 promoter hypermethylation. (bvsalud.org)
Similar1
- When the authors expanded their comparison to multiple groups of US Caucasian women, Chinese women living in China had the lowest median ratio of total estrogens to EM while Asian Americans were similar to US whites. (medscape.com)
Total1
- METHODS: Total RNA and protein were isolated from RWPE-1 human prostate epithelial cells that were coexposed to arsenic and estrogen for a chronic duration (6 months). (bvsalud.org)
Lack1
- We have successfully employed PFPAs in surface modification, targeting polymeric materials that lack reactive functional groups for surface coupling (23, 24). (monossabios.com)
Role1
- Earlier, we also reported the synergistic effect of arsenic and estrogen on decreased expression of MBD4 genes that play an important role in DNA repair through its DNA glycosylase activity. (bvsalud.org)