Genotoxic effects of estrogens.

@article{Liehr1990GenotoxicEO,
  title={Genotoxic effects of estrogens.},
  author={J. Liehr},
  journal={Mutation research},
  year={1990},
  volume={238 3},
  pages={
          269-76
        }
}
  • J. Liehr
  • Published 1990
  • Biology, Medicine
  • Mutation research
Estrogens are associated with several cancers in humans and are known to induce tumors in rodents. In this review a mechanism of carcinogenesis by estrogens is discussed which features the following key events: (1) Steroid estrogens are metabolized by estrogen 2- and 4-hydroxylases to catecholestrogens. Target organs of estrogen-induced carcinogenesis, hamster kidney or mouse uterus, contain high levels of estrogen 4-hydroxylase activity. Since the methylation of 4-hydroxyestradiol by catechol… Expand
Potential mechanisms of estrogen quinone carcinogenesis.
TLDR
The data suggest that other key protein targets for estrogen o-quinones could be redox-sensitive enzymes (i.e, GST P1-1, QR). Expand
Relative imbalances in the expression of estrogen-metabolizing enzymes in the breast tissue of women with breast carcinoma.
TLDR
In women with breast cancer, estrogen metabolism may be related to altered expression of multiple genes, and unbalances appear to be instrumental in causing excessive formation of catechol estrogen quinones that, by reacting with DNA, initiate the series of events leading to breast cancer. Expand
[Mechanisms of estrogen-induced carcinogenesis--detection of DNA adducts in cultured mammalian cells by 32P-postlabeling].
  • T. Tsutsui
  • Biology, Medicine
  • Nihon yakurigaku zasshi. Folia pharmacologica Japonica
  • 1997
TLDR
Induction of morphological transformation of SHE cells by estrogens correlates well with the ability of estrogens to induce DNA adduct formation, indicating that hormonal carcinogenesis is most likely a result of the interplay of both genetic and epigenetic factors. Expand
Quinoids formed from estrogens and antiestrogens.
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It is shown that quinones and quinone methides can be formed from both estrogens and antiestrogens, which could cause DNA damage directly through the formation of DNA adducts or indirectly through the generation of reactive oxygen species that oxidize DNA. Expand
Is 2-methoxyestradiol an endogenous estrogen metabolite that inhibits mammary carcinogenesis?
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Recent studies on the antitumorigenic and antiangiogenic effects of exogenously administered 2-methoxyestradiol in vitro and in vivo are reviewed and it is suggested that some unique effects of 2-MethoxyESTradiol may be mediated by a specific intracellular effector or receptor that is refractory to the parent hormone, estradiol. Expand
Interactions between hormones and chemicals in breast cancer.
  • S. Safe
  • Biology, Medicine
  • Annual review of pharmacology and toxicology
  • 1998
TLDR
Results of recent studies suggest that chemical-induced modulation of 2- OHE1/16 alpha-OHE1 metabolite ratios is not predictive of xenoestrogens or mammary carcinogens, and it is unlikely that xenoESTrogens contribute significantly to a woman's overall lifetime exposure to estrogens. Expand
Free radical generation by redox cycling of estrogens.
  • J. Liehr, D. Roy
  • Chemistry, Medicine
  • Free radical biology & medicine
  • 1990
TLDR
The in vivo activities of enzymes supporting redox cycling of estrogens and free radical generation is correlated with induction of kidney tumors in Syrian hamsters, suggesting a role of free radicals in the induction of tumors by estrogen. Expand
4-Hydroxyestradiol induces oxidative stress and apoptosis in human mammary epithelial cells: possible protection by NF-kappaB and ERK/MAPK.
TLDR
4-OHE2 caused transient activation of extracellular signal-regulated protein kinases (ERK) involved in transmitting cell survival or death signals and a pharmacological inhibitor of ERK aggravated the 4- OHE2-induced cytotoxicity, supporting the pivotal role of ERk in protecting against catechol estrogen-induced oxidative cell death. Expand
Activation of estrogen receptor-mediated gene transcription by the equine estrogen metabolite, 4-methoxyequilenin, in human breast cancer cells.
TLDR
Comparison of the properties of 4-MeOEN with estradiol (E(2)) in human breast cancer cells showed that 4- MeOEN is a proliferative, estrogenic agent that may contribute to carcinogenesis. Expand
Selective estrogen receptor modulator delivery of quinone warheads to DNA triggering apoptosis in breast cancer cells.
TLDR
The results suggest that DNA damage induced by catechol estrogen metabolites can be amplified in ER(+) cells independent of hormonal activity and gives ER-dependent, enhanced apoptosis in mammary cancer cells of potential application in cancer therapy. Expand
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