Lab Anim Res.  2011 Dec;27(4):265-273. 10.5625/lar.2011.27.4.265.

Diverse animal models to examine potential role(s) and mechanism of endocrine disrupting chemicals on the tumor progression and prevention: Do they have tumorigenic or anti-tumorigenic property?

• Park MA
• Hwang KA
• Choi KC

• KMID: 1444958
• DOI: http://doi.org/10.5625/lar.2011.27.4.265

Abstract

Acting as hormone mimics or antagonists in the interaction with hormone receptors, endocrine disrupting chemicals (EDCs) have the potentials of disturbing the endocrine system in sex steroid hormone-controlled organs and tissues. These effects may lead to the disruption of major regulatory mechanisms, the onset of developmental disorders, and carcinogenesis. Especially, among diverse EDCs, xenoestrogens such as bisphenol A, dioxins, and di(2-ethylhexyl)phthalate, have been shown to activate estrogen receptors (ERs) and to modulate cellular functions induced by ERs. Furthermore, they appear to be closely related with carcinogenicity in estrogen-dependant cancers, including breast, ovary, and prostate cancers. In in vivo animal models, prenatal exposure to xenoestrogens changed the development of the mouse reproductive organs and increased the susceptibility to further carcinogenic exposure and tumor occurence in adults. Unlike EDCs, which are chemically synthesized, several phytoestrogens such as genistein and resveratrol showed chemopreventive effects on specific cancers by contending with ER binding and regulating normal ER action in target tissues of mice. These results support the notion that a diet containing high levels of phytoestrogens can have protective effects on estrogen-related diseases. In spite of the diverse evidences of EDCs and phytoestrogens on causation and prevention of estrogen-dependant cancers provided in this article, there are still disputable questions about the dose-response effect of EDCs or chemopreventive potentials of phytoestrogens. As a wide range of EDCs including phytoestrogens have been remarkably increasing in the environment with the rapid growth in our industrial society and more closely affecting human and wildlife, the potential risks of EDCs in endocrine disruption and carcinogenesis are important issues and needed to be verified in detail.

Keyword

Endocrine disrupting chemicals; estrogen; cancer progression; estrogen receptor

MeSH Terms

Adult
Animals
Benzhydryl Compounds
Breast
Diet
Dioxins
Endocrine Disruptors
Endocrine System
Estrogens
Female
Genistein
Humans
Mice
Models, Animal
Ovary
Phenols
Phytoestrogens
Prostatic Neoplasms
Receptors, Estrogen
Stilbenes
Benzhydryl Compounds
Dioxins
Endocrine Disruptors
Estrogens
Genistein
Phenols
Phytoestrogens
Receptors, Estrogen
Stilbenes

Figure

• 

  Figure 1 Genomic pathways of estrogen and EDCs in ER-dependent signaling mechanisms. Estrogen and EDCs can lead to cell proliferation in the genomic pathway in which ER dimers directly bind to EREs following ligands binding or ERs interact with other transcription factors (TFs), including AP-1, by action of transcription factor cross-talk. EDCs can compete with estrogen in ERs binding and induce estrogenic effects.

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