Interactions of Carcinogenic Estrogens with Microtubular Proteins

Chapter 4: Estrogens as Endogenous Genotoxic Agents--DNA Adducts and Mutations

“…Formation of oxygen-free radicals by redox cycling of estrogens or DNA modification by reactive estrogen metabolites may explain some of the structural and numeric chromosomal changes observed in response to estrogen exposure (131,132). Damage to DNA by ROS generated by estrogen treatment, i.e., 8-OHdG, lipid-DNA adducts, and DNA strand breaks, may induce structural and numeric alterations in chromosomes and may be important lesions capable of producing mutagenic changes in the genome.…”

“…For instance, estrogens induce numeric changes in chromosomes (genome mutation or aneuploidy) with and without apparent DNA damage (131). Both DES and E 2 are potent inhibitors of mitosis in vitro and are capable of inducing genomic mutations in cultured cells (132). Potential targets for numeric changes in chromosomes are the spindle apparatus (microtubules and centrioles), DNA, regulating proteins, and centromere.…”

Untangling the association between environmental endocrine disruptive chemicals and the etiology of male genitourinary cancers

“…These metabolites are able to bind to steroid hormone receptors and are electrophilic to DNA [36]. Further, DES as well as its oxidative metabolites affect microtubule proteins by disrupting the mitotic spindle, which leads to aneuploidy [37]. Aneuploidy and DNA adduct formation correlate with DES-induced cell transformation and are considered to be important in DES-induced carcinogenesis [38].…”

“…Sodium/iodine symporter on thyrocytes [91] Hypothalamic-Pituitary-Thyroid [15,93] T 4 conversion to T 3 by deiodinase [96] MAPK signaling cascade [15,30,98] DNA methylation [19,22,23] Aryl hydrocarbon receptor [1] Receptors of neurotransmitter neuronal cells: noradrenergic, serotonergic, dopaminergic [92] Hypothalamic-Pituitary-Adrenal [94] Lipogenesis, lipolysis, and adipogenesis [26,97] cAMP and adenylate cyclase, calcium, PI3K, PKB, Src [19] Histone acetylation [101] Endothelial nitric oxide synthase [98] DNA replication [29,32,37,38,69,70,72] Table 2:…”