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Nathan Goodyear

Potential Mechanisms of Estrogen Quinone Carcinogenesis - 0 views

www.ncbi.nlm.nih.gov/...PMC2556295

estrogen metabolites estrogen quinones 4-OH-estrone cancer hormones

shared by Nathan Goodyear on 19 Sep 15 - No Cached
  • 4-hydroxyestrone/estradiol was found to be carcinogenic in the male Syrian golden hamster kidney tumor model, whereas, 2-hydroxylated metabolites were without activity
  • 4-hydroxyestradiol induced uterine tumors in 66% of CD-1 mice; whereas, mice treated with 2-hydroxyestradiol or 17β-estradiol had much lower uterine tumor incidence
  • DNA adducts of catechol estrogen quinones have been detected in the mammary glands of ACI rats treated with 4-hydroxyestradiol or it’s quinone
  • Nathan Goodyear on 19 Sep 15
     
    great read on the proposed mechanisms of how estrogen metabolites produce quinone intermediates that are carcinogenic.
Nathan Goodyear

Urinary Estrogens and Estrogen Metabolites and Subsequent Risk of Breast Cancer among P... - 0 views

cancerres.aacrjournals.org/...696.full

estrogen metabolites estrogen metabolism ER estrogen receptors ROS hormones cancer breast cancer

shared by Nathan Goodyear on 07 Oct 15 - No Cached
  • both 2- and 4-catechol estrogen metabolites bind to the ER with affinities comparable with estradiol, 4-catechol estrogen metabolites have lower dissociation rates than estradiol and an enhanced ability to upregulate ER-dependent processes
  • 2-catechol estrogen metabolites act as either weak mitogens (39) or weak inhibitors of cell proliferation
  • While 16α-hydroxyestrone binds to the ER with lower affinity than estradiol, it binds covalently (41) and leads to a constitutively activated ER
  • ...15 more annotations...
  • 4-hydroxyestradiol and 16α-hydroxyestrone increasing proliferation and decreasing apoptosis in a manner similar to estradiol; however, these effects were achieved only at concentrations 10-fold higher than estradiol (39). In contrast, 2-hydroxyestradiol did not have substantial proliferative or antiapoptotic effects
  • In our study, the associations with both 2-hydroxyestrone and 16α-hydroxyestrone were nonsignificantly inverse and we did not observe a consistent trend or significant associations between the 2-hydroxyestrone:16α-hydroxyestrone ratio and breast cancer risk
  • Ratios of the 3 hydroxylation pathways were not significantly associated with risk although the 2:16-pathway and 4:16-pathway ratios were suggestively inversely associated
  • a significant inverse association with the ratio of parent estrogens to estrogen metabolites
  • several potentially estrogenic and genotoxic mechanisms
  • Estrogen metabolites also can be genotoxic
  • Catechol estrogens can be oxidized into quinones and induce DNA damage directly through the formation of DNA adducts, or indirectly via redox cycling and generation of reactive oxygen species
  • the oxidized forms of the catechol estrogens differ in their ability to damage DNA through adducts, with oxidized 2-catechols forming stable and reversible DNA adducts and oxidized 4-catechols forming unstable adducts, which lead to depurination and mutations
  • 2- and 4-catechols have been shown to produce reactive oxygen species and induce oxidative DNA damage
  • act independently from the ER
  • 16α-Hydroxyestrone also may be genotoxic
  • While the catechol estrogens have estrogenic and genotoxic potential, the methylated catechol estrogens, which are catechol estrogens with one hydroxyl group methylated, have been hypothesized to lower the risk of breast cancer
  • The suggested mechanisms are indirect, by decreasing circulating levels of catechol estrogens and thereby the opportunity for catechols to exert genotoxic or proliferative effects, or direct, by inhibiting tumor growth and inducing apoptosis
  • the balance between phase I (oxidation) and phase II (methylation) metabolism of estrogen may be important in hormonally related cancer development.
  • Despite the estrogenic and genotoxic potential of many of the estrogen metabolites, we only observed a significantly increased breast cancer risk with one estrogen metabolite, 17-epiestriol, which has particularly strong estrogenic activity and binds to both ERα and ERβ with an affinity comparable with estradiol
  • Nathan Goodyear on 07 Oct 15
     
    review of estrogen metabolites and breast cancer risk in premenopausal women.
Nathan Goodyear

Catechol estrogen metabolites and conjugates in different regions of the prostate of No... - 1 views

carcin.oxfordjournals.org/...329.long

estrogen metabolites prostate cancer COMT GSH estrogen 4-hydroxyestradiol

shared by Nathan Goodyear on 17 Jul 15 - No Cached
  • Nathan Goodyear on 17 Jul 15
     
    loss of ability to handle estrogen quinone metabolites is due to decreased detoxification capacity i.e.COMT, GSH...is associated with prostate carcinogenesis in rats.
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