Endocrine Disrupting Chemicals and Endometrial Cancer: An Overview of Recent Laboratory Evidence and Epidemiological Studies
Abstract
:1. Introduction
2. Polychlorinated Biphenyls and Endometrial Cancer
3. BPA and Endometrial Cancer
4. Dioxins and Endometrial Cancer
5. Cadmium and Endometrial Cancer
6. Conclusions
- Difficulty in the evaluation of the lifelong exposure (e.g., non persistent EDs like most pesticides, phtalates and BPA do not cause a body burden, thus, measuring the level of the substance may not reflect the possible relationship between exposure and slow-onset of the diseases such as cancer);
- Lipophilic EDCs are stored in the fat tissue with a bio-accumulation of minimal daily doses, therefore its rapid mobilization during a drastic diet can expose the person to high doses of the chemical which are not well evaluated in the studies;
- EDCs can have effects at low doses that are not predicted by effects at higher doses (it cannot be assumed that there is a threshold because hormones can regulate the hormone receptors expression resulting in an inverted U dose-response curve); NMDR can arise from numerous molecular mechanisms such as opposing effects induced by multiple receptors differing by their affinity, receptor desensitization, negative feedback with increasing dose, or dose-dependent metabolism modulation;
- Individuals can be concurrently exposed to different EDCs (cocktail effect) generating unpredictable interactions, because the epigenetic effects can also affect future generations especially if the exposure had been in vulnerable developmental periods (e.g., pre-natal and pubertal periods); EDCs are associated with declining human reproductive health, as well as an increasing incidence of cancers of the reproductive system. Verifying such links requires animal models exposed to “real-life”, environmentally relevant concentrations/mixtures of EDC, particularly in utero, when sensitivity to EDC exposure is maximal;
- Some individuals can have a particular susceptibility to ED carcinogenesis;
- It’s not always evaluated that EDCs can also have indirect effects on carcinogen metabolism, immune system, oxidation and inflammation;
- The competing interests may limit research and public information on ED effects.
Author Contributions
Conflicts of Interest
References
- Damstra, T.; Barlow, S.; Bergman, A.; Kavlock, R.J.; Van der Kraak, G. Global assessment of the state-of-the-science of endocrine disruptors. In International Programme on Chemical Safety; World Health Organization: Geneva, Switzerland, 2002. [Google Scholar]
- La Rocca, C.; Tait, S.; Guerranti, C.; Busani, L.; Ciardo, F.; Bergamasco, B.; Perra, G.; Mancini, F.R.; Marci, R.; Bordi, G.; et al. Exposure to Endocrine Disruptors and Nuclear Receptors Gene Expression in Infertile and Fertile Men from Italian Areas with Different Environmental Features. Int. J. Environ. Res. Public Health 2015, 12, 12426–12445. [Google Scholar] [CrossRef] [PubMed]
- Caserta, D.; Bordi, G.; Di Segni, N.; D’Ambrosio, A.; Mallozzi, M.; Moscarini, M. The influence of cigarette smoking on a population of infertile men and women. Arch. Gynecol. Obstet. 2013, 287, 813–818. [Google Scholar] [CrossRef] [PubMed]
- Cancer Incidence for Common Cancers. Available online: http://www.cancerresearchuk.org/cancer-info/cancerstats/incidence/commoncancers/uk-cancer-incidence-statistics-for-common-cancers#Top3 (accessed on August 2013).
- Bergman, A.; Heindel, J.J.; Kasten, T.; Kidd, K.A.; Jobling, S.; Neira, M.; Zoeller, R.T.; Becher, G.; Bjerregaard, P.; Bornman, R.; et al. The impact of endocrine disruption: A consensus statement on the state of the science. Environ. Health Perspect. 2013, 121, A104–A106. [Google Scholar] [CrossRef] [PubMed]
- Balabanic, D.; Rupnik, M.; Klemencic, A.K. Negative impact of endocrine disrupting compounds on human reproductive health. Reprod. Fertil. Dev. 2011, 23, 403–416. [Google Scholar] [PubMed]
- Zelieann, R.C.; Wei, W.; Jodi, A. Flaws endocrine-disrupting chemicals in ovarian function: Effects on steroidogenesis. Metab. Nuclear Recept. Signal. 2011, 142, 633–646. [Google Scholar]
- Birnbaum, L.S.; Fenton, S.E. Cancer and developmentalexposure to endocrine disruptors. Environ. Health Perspect. 2003, 111, 389–394. [Google Scholar] [CrossRef] [PubMed]
- Gibson, D.A.; Saunders, P.T. Endocrinedisruption of oestrogen action and female reproductive tract cancers. Endocr. Relat. Cancer 2014, 21, T13–T31. [Google Scholar] [CrossRef] [PubMed]
- Boon, W.C.; Chow, J.D.; Simpson, E.R. The multiple roles of estrogens and the enzyme aromatase. Prog. Brain Res. 2010, 181, 209–232. [Google Scholar] [PubMed]
- Conzen, S.D. Minireview: Nuclear receptors and breast cancer. Mol. Endocrinol. 2008, 22, 2215–2228. [Google Scholar] [CrossRef] [PubMed]
- Folkerd, E.J.; Dowsett, M. Influence of sex hormones on cancer progression. J. Clin. Oncol. 2010, 28, 4038–4044. [Google Scholar] [CrossRef] [PubMed]
- Knower, K.C.; To, S.Q.; Leung, Y.K.; Ho, S.M.; Clyne, C.D. Endocrine disruption of the epigenome: A breast cancer link. Endocr. Relat. Cancer 2014, 21, T33–T55. [Google Scholar] [CrossRef] [PubMed]
- Russel, L.B.; Hunsicker, P.R.; Cacheiro, N.L.; Bangham, J.W.; Russel, W.L.; Shelby, M.D. Chlorambucil effectively induces deletion mutations in mouse germ cells. Proc. Natl. Acad. Sci. USA 1989, 86, 3704–3708. [Google Scholar] [CrossRef]
- Russel, L.B.; Hunsicker, P.R.; Shelby, M.D. Melphalan, a second chemical for which specific-locus mutation induction in the mouse is maximum in early spermatids. Mutat. Res. 1992, 282, 151–158. [Google Scholar] [CrossRef]
- Oey, H.; Whitelaw, E. On the meaning of the word “epimutation”. Trends Genet. 2014, 30, 519–520. [Google Scholar] [CrossRef] [PubMed]
- Skinner, M.K.; Manikkam, M.; Guerrero-Bosagna, C. Epigenetic transgenerational actions of environmental factors in disease etiology. Trends Endocrinol. Metab. 2010, 21, 214–222. [Google Scholar] [CrossRef] [PubMed]
- Klinge, C.M. Responses miRNAs regulated by estrogens, tamoxifen, and endocrine disruptors and their downstream gene targets. Mol. Cell. Endocrinol. 2015, 418, 273–297. [Google Scholar] [CrossRef] [PubMed]
- Rochester, J.R. Bisphenol A and human health: A review of the literature. Reprod. Toxicol. 2013, 42, 132–155. [Google Scholar] [CrossRef] [PubMed]
- Nordeen, S.K.; Bona, B.J.; Jones, D.N.; Lambert, J.R.; Jackson, T.A. Endocrine disrupting activities of the flavonoid nutraceuticals luteolin and quercetin. Horm. Cancer 2013, 4, 293–300. [Google Scholar] [CrossRef] [PubMed]
- Kortenkamp, A. Are cadmium and other heavy metal compounds acting as endocrinedisrupters? Met. Ions Life Sci. 2011, 8, 305–317. [Google Scholar] [PubMed]
- Boehme, K.; Simon, S.; Mueller, S.O. Gene expression profiling in Ishikawa cells: A fingerprint for estrogen active compounds. Toxicol. Appl. Pharmacol. 2009, 236, 85–96. [Google Scholar] [CrossRef] [PubMed]
- Xu, H.; Kraus, W.L.; Shuler, M.L. Development of a stable dual cell-line GFP expression system to study estrogenic endocrine disruptors. Biotechnol. Bioeng. 2008, 101, 1276–1287. [Google Scholar] [CrossRef] [PubMed]
- Caserta, D.; Maranghi, L.; Mantovani, A.; Marci, R.; Maranghi, F.; Moscarini, M. Impact of endocrine disruptor chemicals in gynaecology. Hum. Reprod. Update 2008, 14, 59–72. [Google Scholar] [CrossRef] [PubMed]
- Singleton, D.W.; Feng, Y.; Yang, J.; Puga, A.; Lee, A.V.; Khan, S.A. Gene expression profiling reveals novel regulation by bisphenol-A in estrogen receptor-alpha-positive human cells. Environ. Res. 2006, 100, 86–92. [Google Scholar] [CrossRef] [PubMed]
- Hardell, L.; van Bavel, B.; Lindström, G.; Björnfoth, H.; Orgum, P.; Carlberg, M.; Sörensen, C.S.; Graflund, M. Adipose tissue concentrations of p,p’-DDE and the risk for endometrial cancer. Gynecol. Oncol. 2004, 95, 706–711. [Google Scholar] [CrossRef] [PubMed]
- Safe, S.; Wang, F.; Porter, W.; Duan, R.; McDougal, A. Ah receptor agonists as endocrine disruptors: Antiestrogenic activity and mechanisms. Toxicol. Lett. 1998, 102–103, 343–347. [Google Scholar] [CrossRef]
- Garey, J.; Wolff, M.S. Estrogenic and antiprogestagenic activities of pyrethroid insecticides. Biochem. Biophys. Res. Commun. 1998, 251, 855–859. [Google Scholar] [CrossRef] [PubMed]
- Caserta, D.; Matteucci, E.; Ralli, E.; Mallozzi, M.; Bordi, G.; Moscarini, M. A 29-year-old woman with complex atypical hyperplasia and polycystic ovary syndrome: A challenging issue. Eur. J. Gynaecol. Oncol. 2014, 35, 97–99. [Google Scholar] [PubMed]
- Skinner, M.K.; Manikkan, M.; Guerrero-Bosagna, C. Epigenetic transgenerational actions of endocrine disruptors. Reprod. Toxicol. 2011, 31, 337–343. [Google Scholar] [CrossRef] [PubMed]
- Vandenberg, L.N.; Colborn, T.; Hayes, T.B.; Heindel, J.J.; Jacobs, D.H., Jr.; Lee, D.H.; Shioda, T.; Soto, A.M.; Vom Saal, F.S.; Welshons, W.V.; et al. Hormones and endocrine-disrupting chemicals: Low-dose effects and nonmonotonic dose. Endocr. Rev. 2012, 33, 378–455. [Google Scholar] [CrossRef] [PubMed]
- Safe, S.H. Is there an association between exposure to environmental estrogens and breast cancer? Environ. Health Perspect. 1997, 105, 675–678. [Google Scholar] [CrossRef] [PubMed]
- Safe, S.H.; Zacharewski, T. Organochlorine exposure and risk for breast cancer. Prog. Clin. Biol. Res. 1997, 396, 133–145. [Google Scholar] [PubMed]
- Brouwer, A.; Longnecker, M.P.; Birnbaum, L.S.; Cogliano, J.; Kostyniak, P.; Moore, J.; Schantz, S.; Winneke, G. Characterization of potential endocrine-related health effects at low-dose levels of exposure to PCBs. Environ. Health Perspect. 1999, 107, 639–649. [Google Scholar] [CrossRef] [PubMed]
- Davidson, N.E. Environmental estrogens and breast cancer risk. Curr. Opin. Oncol. 1998, 10, 475–478. [Google Scholar] [CrossRef] [PubMed]
- Gladen, B.C.; Monaghan, S.C.; Lukyanova, E.M.; Hulchiy, O.P.; Shkyryak-Nyzhnyk, Z.A.; Sericano, J.L.; Little, R.E. Organochlorines in breast milk from two cities in Ukraine. Environ. Health Perspect. 1999, 107, 459–462. [Google Scholar] [CrossRef] [PubMed]
- Little, R.E.; Monaghan, S.C.; Gladen, B.C.; Shkyryak-Nyzhnyk, Z.A.; Wilcox, A.J. Outcomes of 17,137 pregnancies in 2 urban areas of Ukraine. Am. J. Public Health 1999, 89, 1832–1836. [Google Scholar] [CrossRef] [PubMed]
- Baker, V.A. Endocrine disrupters—Testing strategies to assess human hazard. Toxicol. In Vitro 2001, 15, 413–419. [Google Scholar] [CrossRef]
- Nicolopoulou-Stamati, P.; Pitsos, M.A. The impact of endocrine disrupters on the female reproductive system. Hum. Reprod. Update 2001, 7, 323–330. [Google Scholar] [CrossRef] [PubMed]
- Choi, W.; Eum, S.Y.; Lee, Y.W.; Hennig, B.; Robertson, L.W.; Toborek, M. PCB 104-induced proinflammatory reactions in human vascular endothelial cells: Relationship to cancer metastasis and atherogenesis. Toxicol. Sci. 2003, 75, 47–56. [Google Scholar] [CrossRef] [PubMed]
- Eum, S.Y.; Lee, Y.W.; Hennig, B.; Toborek, M. VEGF regulates PCB 104-mediated stimulation of permeability and transmigration of breast cancer cells in human microvascular endothelial cells. Exp. Cell Res. 2004, 296, 231–244. [Google Scholar] [CrossRef] [PubMed]
- Hennig, B.; Hammock, B.D.; Slim, R.; Toborek, M.; Saraswathi, V.; Robertson, L.W. PCB-induced oxidative stress in endothelial cells: Modulation by nutrients. Int. J. Hyg. Environ. Health 2002, 205, 95–102. [Google Scholar] [CrossRef] [PubMed]
- Castro-Rivera, E.; Wormke, M.; Safe, S. Estrogen and arylhydrocarbon responsiveness of ECC-1 endometrial cancer cells. Mol. Cell. Endocrinol. 1999, 150, 11–21. [Google Scholar] [CrossRef]
- Pejić, S.; Todorović, A.; Stojiljković, V.; Cvetković, D.; Lucić, N.; Radojicić, R.M.; Saicić, Z.S.; Pajović, S.B. Superoxide dismutase and lipid hydroperoxides in blood and endometrial tissue of patients with benign, hyperplastic and malignant endometrium. An. Acad. Bras. Cienc. 2008, 80, 515–522. [Google Scholar] [PubMed]
- Chen, Y.; Huang, Q.; Chen, Q.; Lin, Y.; Sun, X.; Zhang, H.; Zhu, M.; Dong, S. The inflammation and estrogen metabolism impacts of polychlorinated biphenyls on endometrial cancer cells. Toxicol. In Vitro 2015, 29, 308–313. [Google Scholar] [CrossRef] [PubMed]
- Zhu, Y.; Kalen, A.L.; Li, L.; Lehmler, H.J.; Robertson, L.W.; Goswami, P.C.; Spitz, D.R.; Aykin-Burns, N. Polychlorinated-biphenyl-induced oxidative stress and cytotoxicity can be mitigated by antioxidants after exposure. Free Radic. Biol. Med. 2009, 47, 1762–1771. [Google Scholar] [CrossRef] [PubMed]
- Arcaro, K.F.; Yi, L.; Seegal, R.F.; Vakharia, D.D.; Yang, Y.; Spink, D.C.; Brosch, K.; Gierthy, J.F. 2,2′,6,6′-Tetrachlorobiphenyl is estrogenic in vitro and in vivo. J. Cell. Biochem. 1999, 72, 94–102. [Google Scholar] [CrossRef]
- Hany, J.; Lilienthal, H.; Sarasin, A.; Roth-Harer, A.; Fastabend, A.; Dunemann, L.; Lichtensteiger, W.; Winneke, G. Developmental exposure of rats to a reconstituted PCB mixture or Aroclor 1254: Effects on organ weights, aromatase activity, sex hormone levels, and sweet preference behavior. Toxicol. Appl. Pharmacol. 1999, 158, 231–243. [Google Scholar] [CrossRef] [PubMed]
- Shekhar, P.V.; Werdell, J.; Basrur, V.S. Environmental estrogen stimulation of growth and estrogen receptor function in preneoplastic and cancerous human breast cell lines. J. Natl. Cancer Inst. 1997, 89, 1774–1782. [Google Scholar] [CrossRef] [PubMed]
- Lind, P.M.; Eriksen, E.F.; Sahlin, L.; Edlund, M.; Orberg, J. Effects of the antiestrogenic environmental pollutant 3,3′,4,4′,5-pentachlorobiphenyl (PCB #126) in rat bone and uterus: Diverging effects in ovariectomized and intact animals. Toxicol. Appl. Pharmacol. 1999, 154, 236–244. [Google Scholar] [PubMed]
- Ramamoorthy, K.; Vyhlidal, C.; Wang, F.; Chen, I.; Safe, S.; McDonnell, D.P.; Leonard, L.S.; Gaido, K.W. Additive estrogenic activities of a binary mixture of 2′,4′,6′-trichloro- and 2′,3′,4′,5′-tetra-chloro-4-biphenylol. Toxicol. Appl. Pharmacol. 1997, 147, 93–100. [Google Scholar] [CrossRef] [PubMed]
- Ahlborg, U.G.; Lipworth, L.; Titus-Ernstoff, L.; Hsieh, C.C.; Hanberg, A.; Baron, J.; Trichopoulos, D.; Adami, H.O. Organochlorine compounds in relation to breast cancer, endometrial cancer, and endometriosis: An assessment of the biological and epidemiological evidence. Crit. Rev. Toxicol. 1995, 25, 463–531. [Google Scholar] [CrossRef] [PubMed]
- Adami, H.O.; Lipworth, L.; Titus-Ernstoff, L.; Hsieh, C.C.; Hanberg, A.; Ahlborg, U.; Baron, J.; Trichopoulos, D. Organochlorine compounds and estrogen-related cancers in women. Cancer Causes Control 1995, 6, 551–566. [Google Scholar] [CrossRef] [PubMed]
- Sturgeon, S.R.; Brock, J.W.; Potischman, N.; Needham, L.L.; Rothman, N.; Brinton, L.A.; Hoover, R.N. Serum concentrations of organochlorine compounds and endometrial cancer risk (United States). Cancer Causes Control 1998, 9, 417–424. [Google Scholar] [CrossRef] [PubMed]
- Yoshizawa, K.; Brix, A.E.; Sells, D.M.; Jokinen, M.P.; Wyde, M.; Orzech, D.P.; Kissling, G.E.; Walker, N.J.; Nyska, A. Reproductive lesions in female Harlan Sprague-Dawley rats following two-year oral treatment with dioxin and dioxin-like compounds. Toxicol. Pathol. 2009, 37, 921–937. [Google Scholar] [CrossRef] [PubMed]
- Reich, O.; Regauer, S.; Scharf, S. High levels of xenoestrogens in patients with low-grade endometrial stromal sarcoma—Report of two cases. Eur. J. Gynaecol. Oncol. 2010, 31, 105–106. [Google Scholar] [PubMed]
- Weiderpass, E.; Adami, H.O.; Baron, J.A.; Wicklund-Glynn, A.; Aune, M.; Atuma, S.; Persson, I. Organochlorines and endometrial cancer risk. Cancer Epidemiol. Biomarkers Prev. 2000, 9, 487–493. [Google Scholar] [PubMed]
- Caserta, D.; Di Segni, N.; Mallozzi, M.; Giovanale, V.; Mantovani, A.; Marci, R.; Moscarini, M. Bisphenol A and the female reproductive tract: An overview of recent laboratory evidence and epidemiological studies. Reprod. Biol. Endocrinol. 2014, 12, 37. [Google Scholar] [CrossRef] [PubMed]
- Newbold, R.R.; Jefferson, W.N.; Padilla-Banks, E. Long-term adverse effects of neonatal exposure to bisphenol A on the murine female reproductive tract. Reprod. Toxicol. 2007, 24, 253–258. [Google Scholar] [CrossRef] [PubMed]
- Kwekel, J.C.; Forgacs, A.L.; Burgoon, L.D.; Williams, K.J.; Zacharewski, T.R. Tamoxifen-elicited uterotrophy: Cross-species and cross-ligand analysis of the gene expression program. BMC Med. Genom. 2009, 2, 19. [Google Scholar] [CrossRef] [PubMed]
- Wang, K.H.; Kao, A.P.; Chang, C.C.; Lin, T.C.; Kuo, T.C. Bisphenol A-induced epithelial to mesenchymal transition is mediated by cyclooxygenase-2 up-regulation in human endometrial carcinoma cells. Reprod. Toxicol. 2015, 58, 229–233. [Google Scholar] [CrossRef] [PubMed]
- Bergeron, R.M.; Thompson, T.B.; Leonard, L.S.; Pluta, L.; Gaido, K.W. Estrogenicity of bisphenol A in a human endometrial carcinoma cell line. Mol. Cell. Endocrinol. 1999, 150, 179–187. [Google Scholar] [CrossRef]
- Gertz, J.; Reddy, T.E.; Varley, K.E.; Garabedian, M.J.; Myers, R.M. Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012, 22, 2153–2162. [Google Scholar] [CrossRef] [PubMed]
- Lee, S.; Suk, K.; Kim, I.K.; Jang, I.S.; Park, J.W.; Johnson, V.J.; Kwon, T.K.; Choi, B.J.; Kim, S.H. Signaling pathways of bisphenol A-induced apoptosis in hippocampal neuronal cells: Role of calcium-induced reactive oxygen species, mitogen-activated protein kinases, and nuclear factor-κB. J. Neurosci. Res. 2008, 86, 2932–2942. [Google Scholar] [CrossRef] [PubMed]
- Masuno, H.; Iwanami, J.; Kidani, T.; Sakayama, K.; Honda, K. Bisphenol A accelerates terminal differentiation of 3T3-L1 cells into adipocytes through the phosphatidylinositol 3-kinase pathway. Toxicol. Sci. 2005, 84, 319–327. [Google Scholar] [CrossRef] [PubMed]
- Kurosawa, T.; Hiroi, H.; Tsutsumi, O.; Ishikawa, T.; Osuga, Y.; Fujiwara, T.; Inoue, S.; Muramatsu, M.; Momoeda, M.; Taketani, Y. The activity of bisphenol A depends on both the estrogen receptor subtype and the cell type. Endocr. J. 2002, 49, 465–471. [Google Scholar] [CrossRef] [PubMed]
- Klotz, D.M.; Hewitt, S.C.; Korach, K.S.; Diaugustine, R.P. Activation of a uterine insulin-like growth factor I signaling pathway by clinical and environmental estrogens: Requirement of estrogen receptor-alpha. Endocrinology 2000, 141, 3430–3439. [Google Scholar] [PubMed]
- Schug, T.T.; Janesick, A.; Blumberg, B.; Heindel, J.J. Endocrine disrupting chemicals and disease susceptibility. J. Steroid Biochem. Mol. Biol. 2011, 27, 204–215. [Google Scholar] [CrossRef] [PubMed]
- Sheehan, D.M. Activity of environmentally relevant low doses of endocrine disruptors and the bisphenol A controversy: Initial results confirmed. Proc. Soc. Exp. Biol. Med. 2000, 224, 57–60. [Google Scholar] [CrossRef] [PubMed]
- Mileva, G.; Baker, S.L.; Konkle, A.T.; Bielajew, C. Bisphenol-A: Epigenetic reprogramming and effects on reproduction and behavior. Int. J. Environ. Res. Public Health 2014, 11, 7537–7561. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Luh, C.J.; Burns, K.A.; Arao, Y.; Jiang, Z.; Teng, C.T.; Tice, R.R.; Korach, K.S. Endocrine-disrupting chemicals (EDCs): In vitro mechanism of estrogenic activation and differential effects on ER target genes. Environ. Health Perspect. 2013, 121, 459–466. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Burns, K.A.; Arao, Y.; Luh, C.J.; Korach, K.S. Differential estrogenic actions of endocrine-disrupting chemicals bisphenol A, bisphenol AF, and zearalenone through estrogen receptor a and b in vitro. Environ. Health Perspect. 2012, 120, 1029–1035. [Google Scholar] [CrossRef] [PubMed]
- Hiroi, H.; Tsutsumi, O.; Takeuchi, T.; Momoeda, M.; Ikezuki, Y.; Okamura, A.; Yokota, H.; Taketani, Y. Differences in serum bisphenol a concentrations in premenopausal normal women and women with endometrial hyperplasia. Endocr. J. 2004, 51, 595–600. [Google Scholar] [CrossRef] [PubMed]
- Rubin, B.S. Bisphenol A: An endocrine disruptor with widespread exposure and multiple effects. J. Steroid Biochem. Mol. Biol. 2011, 127, 27–34. [Google Scholar] [CrossRef] [PubMed]
- Sui, Y.; Ai, N.; Park, S.H.; Rios-Pilier, J.; Perkins, J.T.; Welsh, W.J.; Zhou, C. Bisphenol A and its analogues activate human pregnane X receptor. Environ. Health Perspect. 2012, 120, 399–405. [Google Scholar] [CrossRef] [PubMed]
- Tait, S.; Tassinari, R.; Maranghi, F.; Mantovani, A. Bisphenol A affects placental layers morphology and angiogenesis during early pregnancy phase in mice. J. Appl. Toxicol. 2015, 35, 1278–1291. [Google Scholar] [CrossRef] [PubMed]
- Matsushima, A.; Teramoto, T.; Okada, H.; Liu, X.; Tokunaga, T.; Kakuta, Y.; Shimohigashi, Y. ERRgamma tethers strongly bisphenol A and 4-alpha-cumylphenol in an induced-fit manner. Biochem. Biophys. Res. Commun. 2008, 373, 408–413. [Google Scholar] [CrossRef] [PubMed]
- Fenichel, P.; Chevalier, N.; Brucker-Davis, F. Bisphenol A: An endocrine and metabolic disruptor. Ann. Endocrinol. 2013, 74, 211–220. [Google Scholar] [CrossRef] [PubMed]
- Thomas, P.; Dong, J. Binding and activation of the seven-transmembrane estrogen receptor GPR30 by environmental estrogens: A potential novel mechanism of endocrine disruption. J. Steroid Biochem. Mol. Biol. 2006, 102, 175–179. [Google Scholar] [CrossRef] [PubMed]
- Aghajanova, L.; Giudice, L.C. Effect of bisphenol A on human endometrial stromal fibroblasts in vitro. Reprod. BioMed. Online 2011, 22, 249–256. [Google Scholar] [CrossRef] [PubMed]
- Rezg, R.; El-Fazaa, S.; Gharbi, N.; Mornagui, B. Bisphenol A and human chronic diseases: Current evidences, possible mechanisms, and future perspectives. Environ. Int. 2014, 64, 83–90. [Google Scholar] [CrossRef] [PubMed]
- Ferreira, L.L.; Couto, R.; Oliveira, P.J. Bisphenol A as epigenetic modulator: Setting the stage for carcinogenesis? Eur. J. Clin. Investig. 2015, 45, 32–36. [Google Scholar] [CrossRef] [PubMed]
- Fernandez, S.V.; Huang, Y.; Snider, K.E.; Zhou, Y.; Pogash, T.J.; Russo, J. Expression and DNA methylation changes in human breast epithelial cells after bisphenol A exposure. Int. J. Oncol. 2012, 41, 369–377. [Google Scholar] [CrossRef] [PubMed]
- Gregoraszczuk, E.L. Dioxin exposure and porcine reproductive hormonal activity. Cad. Saude Publica 2002, 18, 453–462. [Google Scholar] [CrossRef] [PubMed]
- Jablonska, O.; Piasecka-Srader, J.; Nynca, A.; Kołomycka, A.; Robak, A.; Wąsowska, B.; Ciereszko, R.E. 2,3,7,8-Tetrachlorodibenzo-p-dioxin alters steroid secretion but does not affect cell viability and the incidence of apoptosis in porcine luteinised granulosa cells. Acta Vet. Hung. 2014, 62, 408–421. [Google Scholar] [CrossRef] [PubMed]
- Agency for Toxic Substances and Disease Registry (ATSDR). Toxicological Profile for Chlorinated Dibenzo-p-Dioxins; Agency for Toxic Substances and Disease Registry: Atlanta, GA, USA, 1998.
- Bertazzi, P.A.; Consonni, D.; Bachetti, S.; Rubagotti, M.; Baccarelli, A.; Zocchetti, C.; Pesatori, A.C. Health effects on dioxin exposure: A 20-year mortality study. Am. J. Epidemiol. 2001, 153, 1031–1044. [Google Scholar] [CrossRef] [PubMed]
- Pesatori, A.C.; Consonni, D.; Bachetti, S.; Zocchetti, C.; Bonzini, M.; Baccarelli, A.; Bertazzi, P.A. Short- and long-term morbidity and mortality in the population exposed to dioxin after the “Seveso accident”. Ind. Health 2003, 41, 127–138. [Google Scholar] [CrossRef] [PubMed]
- Carcinogen Classificationon. Available online: http://www.iarc.fr/ENG/Databases/index.php (accessed on 1 December 2016).
- Pocar, P.; Fischer, B.; Klonisch, T.; Hombach-Klonisch, S. Molecular interactions of the aryl hydrocarbon receptor and its biological and toxicological relevance for reproduction. Reproduction 2005, 129, 379–389. [Google Scholar] [CrossRef] [PubMed]
- Bunger, M.K.; Moran, S.M.; Glover, E.; Thomae, T.L.; Lahvis, G.P.; Lin, B.C.; Bradfield, C.A. Resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity and abnormal liver development in mice carrying a mutation in the nuclear localization sequence of the aryl hydrocarbon receptor. J. Biol. Chem. 2003, 278, 17767–17774. [Google Scholar] [CrossRef] [PubMed]
- Moffat, I.D.; Boutros, P.C.; Chen, H.; Okey, A.B.; Pohjanvirta, R. Aryl hydrocarbon receptor (AHR)-regulated transcriptomic changes in rats sensitive or resistant to major dioxin toxicities. BMC Genom. 2010, 11, 263. [Google Scholar] [CrossRef] [PubMed]
- Petrulis, J.R.; Perdew, G.H. The role of chaperone proteins in the aryl hydrocarbon receptor core complex. Chem. Biol. Interact. 2002, 141, 25–40. [Google Scholar] [CrossRef]
- Boutros, P.C.; Moffat, I.D.; Franc, M.A.; Tijet, N.; Tuomisto, J.; Pohjanvirta, R.; Pohjanvirta, R.; Okey, A.B. Dioxin-responsive AHRE-II gene battery: Identification by phylogenetic footprinting. Biochem. Biophys. Res. Commun. 2004, 321, 707–715. [Google Scholar] [CrossRef] [PubMed]
- Reyes, H.; Reisz-Porszasz, S.; Hankinson, O. Identification of the Ah receptor nuclear translocator protein (Arnt) as a component of the DNA binding form of the Ah receptor. Science 1992, 256, 1193–1195. [Google Scholar] [CrossRef] [PubMed]
- Kociba, R.J.; Keyes, D.G.; Beyer, J.E.; Carreon, R.M.; Wade, C.E.; Dittenber, D.A.; Kalnins, R.P.; Frauson, L.E.; Park, C.N.; Barnard, S.D.; et al. Results of a two-year chronic toxicity and oncogenicity study of 2,3,7,8-tetrachlorodibenzo-p-dioxin in rats. Toxicol. Appl. Pharmacol. 1978, 46, 279–303. [Google Scholar] [CrossRef]
- Biegel, L.; Safe, S. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on cell growth and the secretion of the estrogen-induced 34-, 52- and 160-kDa proteins in human breast cancer cells. J. Steroid Biochem. Mol. Biol. 1990, 37, 725–732. [Google Scholar] [CrossRef]
- Romkes, M.; Safe, S. Comparative activities of 2,3,7,8-tetrachlorodibenzo-p-dioxin and progesterone as antiestrogens in the female rat uterus. Toxicol. Appl. Pharmacol. 1988, 92, 368–380. [Google Scholar] [CrossRef]
- Fries, G.F.; Marrow, G.S. Retention and excretion of 2,3,7,8-tetrachlorodibenzo-p-dioxin by rats. J. Agric. Food Chem. 1975, 23, 265–269. [Google Scholar] [CrossRef] [PubMed]
- Gierthy, J.F.; Lincoln, D.W.; Gillepsie, M.B.; Seeger, J.I.; Martinez, H.L.; Dickerman, H.W.; Kumar, S.A. Suppresion of estrogen-regulated extracellular tissue plasminogen activator activity of MCF-7 cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Cancer Res. 1987, 47, 6189–6203. [Google Scholar]
- Gierthy, J.F.; Lincoln, D.W. Inhibition of postconfluent focus production in cultures of MCF-7 human breast cancer cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Breast Cancer Res. Treat. 1988, 12, 227–233. [Google Scholar] [CrossRef] [PubMed]
- Spink, D.C.; Lincoln, D.W.; Dickerman, H.W.; Gierthy, J.F. 2,3,7,8-Tetrachlorodibenzo-p-dioxin causes an extensive alteration of 17 beta-estradiol metabolism in MCF-7 breast tumor cells. Proc. Natl. Acad. Sci. USA 1990, 87, 6917–6921. [Google Scholar] [CrossRef] [PubMed]
- Döhr, O.; Vogel, C.; Abel, J. Different response of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-sensitive genes in human breast cancer MCF-7 and MDA-MB 231 cells. Arch. Biochem. Biophys. 1995, 321, 405–412. [Google Scholar] [CrossRef] [PubMed]
- Romkes, M.; Piskorska-Pliszczynska, J.; Safe, S. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on hepatic and uterine estrogen receptor levels in rats. Toxicol. Appl. Pharmacol. 1987, 87, 306–314. [Google Scholar] [CrossRef]
- Harris, M.; Zacharewski, T.; Safe, S. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds on the occupied nuclear estrogen receptor in MCF-7 human breast cancer cells. Cancer Res. 1990, 50, 3579–3584. [Google Scholar] [PubMed]
- Wang, X.; Porter, W.; Krishnan, V.; Narasimhan, T.R.; Safe, S. Mechanism of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated decrease of the nuclear estrogen receptor in MCF-7 human breast cancer cells. Mol. Cell. Endocrinol. 1993, 96, 159–166. [Google Scholar] [CrossRef]
- Kharat, I.; Saatcioglu, F. Antiestrogenic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin are mediated by direct transcriptional interference with the liganded estrogen receptor. Cross-talk between aryl hydrocarbon- and estrogen-mediated signaling. J. Biol. Chem. 1996, 271, 10533–10537. [Google Scholar] [PubMed]
- Gillesby, B.E.; Stanostefano, M.; Porter, W.; Safe, S.; Wu, Z.F.; Zacharewski, T.R. Identification of a motif within the 5′ regulatory region of pS2 which is responsible for AP-1 binding and TCDD-mediated suppression. Biochemistry 1997, 36, 6080–6089. [Google Scholar] [CrossRef] [PubMed]
- Sofo, V.; Götte, M.; Laganà, A.S.; Salmeri, F.M.; Triolo, O.; Sturlese, E.; Retto, G.; Alfa, M.; Granese, R.; Abrão, M.S. Correlation between dioxin and endometriosis: An epigenetic route to unravel the pathogenesis of the disease. Arch. Gynecol. Obstet. 2015, 292, 973–986. [Google Scholar] [CrossRef] [PubMed]
- Thompson, P.A.; Khatami, M.; Baglole, C.J.; Sun, J.; Harris, S.A.; Moon, E.Y.; Al-Mulla, F.; Al-Temaimi, R.; Brown, D.G.; Colacci, A.; et al. Environmental immune disruptors, inflammation and cancerrisk. Carcinogenesis 2015, 36, S232–S253. [Google Scholar] [CrossRef] [PubMed]
- Charles, G.D.; Shiverick, K.T. 2,3,7,8-Tetrachlorodibenzo-p-dioxin increases mRNA levels for interleukin-1beta, urokinase plasminogen activator, and tumor necrosis factor-alpha in human uterine endometrial adenocarcinoma RL95-2 cells. Biochem. Biophys. Res. Commun. 1997, 238, 338–342. [Google Scholar] [CrossRef] [PubMed]
- Jana, N.R.; Sarkar, S.; Ishizuka, M.; Yonemoto, J.; Tohyama, C.; Sone, H. Role of estradiol receptor-alpha in differential expression of 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible genes in the RL95–2 and KLE human endometrial cancer cell lines. Arch. Biochem. Biophys. 1999, 368, 31–39. [Google Scholar] [CrossRef] [PubMed]
- Safe, S.; McDougal, A. Mechanism of action and development of selective aryl hydrocarbon receptor modulators for treatment of hormone-dependent cancers (Review). Int. J. Oncol. 2002, 20, 1123–1128. [Google Scholar] [CrossRef] [PubMed]
- Fiorella, P.D.; Olson, J.R.; Napoli, J.L. 2,3,7,8-Tetrachlorodibenzo-p-dioxin induces diverse retinoic acid metabolites in multiple tissues of the Sprague-Dawley rat. Toxicol. Appl. Pharmacol. 1995, 134, 222–228. [Google Scholar] [CrossRef] [PubMed]
- Takemoto, K.; Nakajima, M.; Fujiki, Y.; Katoh, M.; Gonzalez, F.J.; Yokoi, T. Role of the aryl hydrocarbon receptor and CYP1B1 in the antiestrogenic activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. Arch. Toxicol. 2004, 78, 309–315. [Google Scholar] [CrossRef] [PubMed]
- Wormke, M.; Stoner, M.; Saville, B.; Walker, K.; Abdelrahim, M.; Burghardt, R.; Safe, S. The aryl hydrocarbon receptor mediates degradation of estrogen receptor a through activation of proteasomes. Mol. Cell. Biol. 2003, 23, 1843–1855. [Google Scholar] [CrossRef] [PubMed]
- Van Birgelen, A.P.; van der Kolk, J.; Fase, K.M.; Bol, I.; Poiger, H.; Brouwer, A.; van den Berg, M. Subchronic dose-response study of 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Sprague-Dawley rats. Toxicol. Appl. Pharmacol. 1995, 132, 1–13. [Google Scholar] [CrossRef] [PubMed]
- Hakansson, H.; Johansson, L.; Manzoor, E.; Ahlborg, U.G. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the vitamin A status of Hartley guinea pigs, Sprague-Dawley rats, C57Bl/6 mice, DBA/2 mice, and Golden Syrian hamsters. J. Nutr. Sci. Vitaminol. 1991, 37, 117–138. [Google Scholar] [CrossRef] [PubMed]
- Ricci, M.S.; Toscano, D.G.; Mattingly, C.J.; Toscano, W.A., Jr. Estrogen receptor reduces CYP1A1 induction in cultured human endometrial cells. J. Biol. Chem. 1999, 274, 3430–3438. [Google Scholar] [CrossRef] [PubMed]
- Bertazzi, A.; Pesatori, A.C.; Consonni, D.; Tironi, A.; Landi, M.T.; Zocchetti, C. Cancer incidence in a population accidentally exposed to 2,3,7,8-tetrachlorodibenzo-para-dioxin. Epidemiology 1993, 4, 398–406. [Google Scholar] [CrossRef] [PubMed]
- Ray, S.S.; Swanson, H.I. Alteration of keratinocyte differentiation and senescence by the tumor promoter dioxin. Toxicol. Appl. Pharmacol. 2003, 192, 131–145. [Google Scholar] [CrossRef]
- Schmidt, C.K.; Hoegberg, P.; Fletcher, N.; Nilsson, C.B.; Trossvik, C.; Hakansson, H.; Nau, H. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters the endogenous metabolism of all-trans-retinoic acid in the rat. Arch. Toxicol. 2003, 77, 371–383. [Google Scholar] [PubMed]
- Fletcher, N.; Hanberg, A.; Hakansson, H. Hepatic vitamin a depletion is a sensitive marker of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in four rodent species. Toxicol. Sci. 2001, 62, 166–175. [Google Scholar] [CrossRef] [PubMed]
- Hakansson, H.; Manzoor, E.; Trossvik, C.; Ahlborg, U.G.; Chu, I.; Villenueve, D. Effect on tissue vitamin A levels in the rat following subchronic exposure to four individual PCB congeners (IUPAC 77, 118, 126, and 153). Chemosphere 1994, 29, 2309–2313. [Google Scholar] [CrossRef]
- Everts, H.B.; Sundberg, J.P.; Ong, D.E. Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat. Exp. Cell Res. 2005, 308, 309–319. [Google Scholar] [CrossRef] [PubMed]
- Lancillotti, F.; Darwiche, N.; Celli, G.; De Luca, L.M. Retinoid status and the control of keratin expression and adhesion during the histogenesis of squamous mataplasia of tracheal epithelium. Cancer Res. 1992, 52, 6144–6152. [Google Scholar] [PubMed]
- Lotan, R. Suppression of squamous cell carcinoma growth and differentiation by retinoids. Cancer Res. 1994, 54, 1987–1990. [Google Scholar]
- National Toxicology Program. Toxicology and Carcinogenesis Studies of a Mixture of 3,30,4,40,5-pentachlorobiphenyl (PCB126) (CAS No. 57465-28-8) and 2,20,4,40,5,50-Hexachlorobiphenyl (PCB153) (CAS No. 57065-27-1) in Female Harlan Sprague-Dawley Rats (Gavage Studies); NTP TR530; NIEHS: Research Triangle Park, NC, USA, 2004. [Google Scholar]
- Yoshizawa, K.; Walker, N.J.; Jokinen, M.P.; Brix, A.E.; Sells, D.M.; Marsh, T.; Wyde, M.E.; Orzech, D.; Haseman, J.K.; Nyska, A. Gingival carcinogenicity in female Harlan Sprague-Dawley rats following two-year oral treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin and dioxin-like compounds. Toxicol. Sci. 2005, 83, 64–77. [Google Scholar] [CrossRef] [PubMed]
- Soave, I.; Caserta, D.; Wenger, J.M.; Dessole, S.; Perino, A.; Marci, R. Environment and Endometriosis: A toxic relationship. Eur. Rev. Med. Pharmacol. Sci. 2015, 19, 1964–1972. [Google Scholar] [PubMed]
- Kok, V.C.; Tsai, H.J.; Su, C.F.; Lee, C.K. The risks for ovarian, endometrial, breast, colorectal, and other cancers in women with newly diagnosed endometriosis or adenomyosis: A population-based study. Int. J. Gynecol. Cancer 2015, 25, 968–976. [Google Scholar] [CrossRef] [PubMed]
- Ismiil, N.; Rasty, G.; Ghorab, Z.; Nofech-Mozes, S.; Bernardini, M.; Ackerman, I.; Thomas, G.; Covens, A.; Khalifa, M.A. Adenomyosis involved by endometrial adenocarcinoma is a significant risk factor for deep myometrial invasion. Ann. Diagn. Pathol. 2007, 11, 252–257. [Google Scholar] [CrossRef] [PubMed]
- Ismiil, N.D.; Rasty, G.; Ghorab, Z.; Nofech-Mozes, S.; Bernardini, M.; Thomas, G.; Ackerman, I.; Covens, A.; Khalifa, M.A. Adenomyosis is associated with myometrial invasion by FIGO 1 endometrial adenocarcinoma. Int. J. Gynecol. Pathol. 2007, 26, 278–283. [Google Scholar] [CrossRef] [PubMed]
- Hall, J.B.; Young, R.H.; Nelson, J.H., Jr. The prognostic significance of adenomyosis in endometrial carcinoma. Gynecol. Oncol. 1984, 17, 32–40. [Google Scholar] [CrossRef]
- Koshiyama, M.; Okamoto, T.; Ueta, M. The relationship between endometrial carcinoma and coexistent adenomyosis uteri, endometriosis externa and myoma uteri. Cancer Detect. Prev. 2004, 28, 94–98. [Google Scholar] [CrossRef] [PubMed]
- Krawczyk, N.; Banys-Paluchowski, M.; Schmidt, D.; Ulrich, U.; Fehm, T. Endometriosis-associated Malignancy. Geburtshilfe Frauenheilkd 2016, 76, 176–181. [Google Scholar] [CrossRef] [PubMed]
- Agency for Toxic Substances and Disease Registry. Toxicological Profile for Cadmium; U.S. Department of Health and Human Service: Atlanta, GA, USA, 2011.
- Jarup, L.; Akesson, A. Current status of cadmium as an environmental health problem. Toxicol. Appl. Pharmacol. 2009, 238, 201–208. [Google Scholar] [CrossRef] [PubMed]
- Richter, P.A.; Bishop, E.E.; Wang, J.; Swahn, M.H. Tobacco smoke exposure and levels of urinary metals in the U.S. youth and adult population: The National Health and Nutrition Examination Survey (NANHES) 1991–2004. Int. J. Environ. Res. Public Health 2009, 6, 1930–1946. [Google Scholar] [CrossRef] [PubMed]
- Wilhelm, M.; Ewers, U.; Schulz, C. Revised and new reference values for some trace elements in blood and urine for human biomonitoring in environmental medicine. Int. J. Hyg. Environ. Health 2004, 207, 69–73. [Google Scholar] [CrossRef] [PubMed]
- Vahter, M.; Berglund, M.; Akesson, A.; Liden, C. Metals and women’s health. Environ. Res. Sec. A 2002, 88, 145–155. [Google Scholar] [CrossRef] [PubMed]
- Elinder, C.G.; Kjellstrom, T. Carcinogenic and mutagenic effects. In Cadmium and Health: A Toxicological and Epidemiological Appraisal; Friberg, L., Elinder, C.G., Kjellstrom, T., Nordberg, G.F., Eds.; CRC Press: Boca Raton, FL, USA, 1986; pp. 205–229. [Google Scholar]
- Nasiadek, M.; Krawczyk, T.; Sapota, A. Tissue levels of cadmium and trace elements in patients with myoma and uterine cancer. Hum. Exp. Toxicol. 2005, 24, 623–630. [Google Scholar] [CrossRef] [PubMed]
- Jarup, L.; Berglund, M.; Elinder, C.G.; Nordberg, G.; Vahter, M. Health effects of cadmium exposure—A review of the literature and a risk estimate. Scan. J. Work Environ. Health 1998, 24, 1–51. [Google Scholar]
- Stoica, A.; Katzenellenbogen, B.S.; Martin, M.B. Activation of estrogen receptor-α by the heavy metal cadmium. Mol. Endocrinol. 2000, 14, 545–553. [Google Scholar] [PubMed]
- Akesson, A.; Julin, B.; Wolk, A. Long-term dietary cadmium intake and postmenopausal endometrial cancer incidence: A population-based prospective cohort study. Cancer Res. 2008, 68, 6435–6441. [Google Scholar] [CrossRef] [PubMed]
- Nawrot, T.; Plusquin, M.; Hogervorst, J.; Roels, H.A.; Celis, H.; Thijs, L.; Vangronsveld, J.; van Hecke, E.; Staessen, J.A. Environmental exposure to cadmium and risk of cancer: A prospective population-based study. Lancet Oncol. 2006, 7, 119–126. [Google Scholar] [CrossRef]
- Lag, M.; Rodionov, D.; Ovrevik, J.; Bakke, O.; Schwarze, P.E.; Refsnes, M. Cadmium-induced inflammatory responses in cells relevant for lung toxicity: Expression and release of cytokines in fibroblasts, epithelial cells and macrophages. Toxicol. Lett. 2010, 193, 252–260. [Google Scholar] [CrossRef] [PubMed]
- Liu, J.; Qu, W.; Kadiiska, M.B. Role of oxidative stress in cadmium toxicity and carcinogenesis. Toxicol. Appl. Pharmacol. 2009, 238, 209–214. [Google Scholar] [CrossRef] [PubMed]
- Asmuss, M.; Mullenders, L.H.; Hartwig, A. Interference by toxic metal compounds with isolated zinc finger DNA repair proteins. Toxicol. Lett. 2000, 112–113, 227–231. [Google Scholar] [CrossRef]
- Giaginis, C.; Gatzidou, E.; Theocharis, S. DNA repair systems as targets of cadmium toxicity. Toxicol. Appl. Pharmacol. 2006, 213, 282–290. [Google Scholar] [CrossRef] [PubMed]
- Takiguchi, M.; Achanzar, W.E.; Qu, W.; Li, G.; Waalkes, M.P. Effects of cadmium on DNA-(Cytosine-5) methyltransferase activity and DNA methylation status during cadmium-induced cellular transformation. Exp. Cell Res. 2003, 286, 355–365. [Google Scholar] [CrossRef]
- Liu, Z.; Yu, X.; Shaikh, Z.A. Rapid activation of ERK1/2 and AKT in human breast cancer cells by cadmium. Toxicol. Appl. Pharmacol. 2008, 228, 286–294. [Google Scholar] [CrossRef] [PubMed]
- Garcia-Morales, P.; Saceda, M.; Kenney, N.; Kim, N.; Salomon, D.S.; Gottardis, M.M.; Solomon, H.B.; Sholler, P.F.; Jordan, V.C.; Martin, M.B. Effect of cadmium on estrogen receptor levels and estrogen-induced responses in human breast cancer cells. J. Biol. Chem. 1994, 269, 16896–16901. [Google Scholar] [PubMed]
- Johnson, M.D.; Kenney, N.; Stoica, A.; Hilakivi-Clarke, L.; Singh, B.; Chepko, G.; Chepko, G.; Clarke, R.; Sholler, P.F.; Lirio, A.A.; et al. Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland. Nat. Med. 2003, 9, 1081–1084. [Google Scholar] [CrossRef] [PubMed]
- Benbrahim-Tallaa, L.; Tokar, E.J.; Diwan, B.A.; Dill, A.L.; Coppin, J.F.; Waalkes, M.P. Cadmium malignantly transforms normal human breast epithelial cells into a basal-like phenotype. Environ. Health Perspect. 2009, 117, 1847–1852. [Google Scholar] [CrossRef] [PubMed]
- Eriksen, K.T.; Halkjær, J.; Sørensen, M.; Meliker, J.R.; McElroy, J.A.; Tjønneland, A.; Raaschou-Nielsen, O. Dietary cadmium intake and risk of breast, endometrial and ovarian cancer in Danish postmenopausal women: A prospective cohort study. PLoS ONE 2014, 9, e100815. [Google Scholar]
- Adams, S.V.; Quraishi, S.M.; Shafer, M.M.; Passarelli, M.N.; Freney, E.P.; Chlebowski, R.T.; Luo, J.; Meliker, J.R.; Mu, L.; Neuhouser, M.L.; et al. Dietary cadmium exposure and risk of breast, endometrial, and ovarian cancer in the Women’s Health Initiative. Environ. Health Perspect. 2014, 122, 594–600. [Google Scholar] [CrossRef] [PubMed]
- Cho, Y.A.; Kim, J.; Woo, H.D.; Kang, M. Dietary cadmium intake and the risk of cancer: A meta-analysis. PLoS ONE 2013, 8, e75087. [Google Scholar] [CrossRef] [PubMed]
- Yaman, M.; Kaya, G.; Simsek, M. Comparison of trace element concentrations in cancerous and noncancerous human endometrial and ovary tissues. Int. J. Gynecol. Cancer 2007, 17, 220–228. [Google Scholar] [CrossRef] [PubMed]
- Sawada, N.; Iwasaki, M.; Inoue, M.; Takachi, R.; Sasazuki, S.; Yamaji, T.; Shimazu, T.; Endo, Y.; Tsugane, S. Long-term dietary cadmium intake and cancer incidence. Epidemiology 2012, 23, 368–376. [Google Scholar] [CrossRef] [PubMed]
- Julin, B.; Wolk, A.; Åkesson, A. Dietary cadmium exposure and risk of epithelial ovarian cancer in a prospective cohort of Swedish women. Br. J. Cancer 2011, 105, 441–444. [Google Scholar] [CrossRef] [PubMed]
- Adams, S.V.; Newcomb, P.A.; White, E. Dietary cadmium and risk of invasive postmenopausal breast cancer in the VITAL cohort. Cancer Causes Control 2012, 23, 845–854. [Google Scholar] [CrossRef] [PubMed]
- Julin, B.; Wolk, A.; Johansson, J.E.; Andersson, S.O.; Andrén, O.; Akesson, A. Dietary cadmium exposure and prostate cancer incidence: A population-based prospective cohort study. Br. J. Cancer 2012, 107, 895–900. [Google Scholar] [CrossRef] [PubMed]
- Julin, B.; Wolk, A.; Bergkvist, L.; Bottai, M.; Åkesson, A. Dietary cadmium exposure and risk of postmenopausal breast cancer: A population-based prospective cohort study. Cancer Res. 2012, 72, 1459–1466. [Google Scholar] [CrossRef] [PubMed]
- Barker, D.J. The developmental origins of adult disease. J. Am. Coll. Nutr. 2004, 23, S588–S595. [Google Scholar] [CrossRef]
- Skinner, M.K. Endocrine disruptor induction of epigenetic transgenerational inheritance of disease. Mol. Cell. Endocrinol. 2014, 398, 4–12. [Google Scholar] [CrossRef] [PubMed]
Type of Article | Main Author (Year) | Subject |
---|---|---|
Review | Klinge (2015) [18] | miRNAs regulated by estrogens, tamoxifen, and endocrine disruptors and their downstream gene targets. |
Review | Gibson (2015) [9] | Endocrine disruption of oestrogen action and female reproductive tract cancers. |
Review | Rochester (2015) [19] | Bisphenol A and human health: A review of the literature |
In vitro study | Nordeen (2013) [20] | Endocrine disrupting activities of the flavonoid nutraceuticals luteolin and quercetin |
In vitro study | Kortenkamp (2011) [21] | Are cadmium and other heavy metal compounds acting as endocrine disrupters? |
In vitro study | Boehme (2009) [22] | Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds |
In vitro study | Xu (2008) [23] | Development of a stable dual cell-line GFP expression system to study estrogenic endocrine disruptors. |
Review | Caserta (2008) [24] | Impact of endocrine disruptor chemicals in gynaecology. |
In vitro study | Singleton (2006) [25] | Gene expression profiling reveals novel regulation by bisphenol-A in estrogen receptor-alpha-positive human cells. |
Case Control Study | Hardell (2004) [26] | Adipose tissue concentrations of p,p’-DDE and the risk for endometrial cancer. |
In vitro study | Safe (1998) [27] | Ah receptor agonists as endocrine disruptors: antiestrogenic activity and mechanisms. |
In vitro study | Garey (1998) [28] | Estrogenic and antiprogestagenic activities of pyrethroid insecticides. |
Chemical(s) | Pathways of Exposure | Mechanism of Action | Authors (Year) | Results |
---|---|---|---|---|
Polychlorinated biphenyls (PCBs) | Food chain (fat-rich food, e.g., milk and derivates, fatty fish), living environment | Alteration steroid hormone metabolism/transport, ability to bind with the tyroxin transport protein transthyretin (TTR), interaction with thyroid hormone receptors, neuroendocrine effects. PCBs dioxin-like: Aril hydrocarbon Receptor interaction leading to altered steroid hormone metabolism and neuroendocrine effects including on thyroid | Chen, et al. 2015 [45] | It was observed that PCBs affected the expression of inflammatory factors through ER and AHR receptors but no toxic effects were observed on estrogen metabolism. |
Reich, et al. 2010 [56] | Case Control Study where high levels of PCB and others EDCs where found in the abdominal adipose tissue of two cases of endometrial stromal sarcoma | |||
Yoshizawa, K. et al. 2009 [55] | In vivo study where female adult Harlan Sprague-Dawley rats were exposed for 14, 31 or 53 weeks or for two years to different EDCs including PCB126, PeCDF, PCB153, PCB118, a binary mixture of PCB126 and 153; or a binary mixture of PCB126 and PCB118; and resulted in an increasing of uterine squamous cell carcinoma uterine squamous cell carcinoma in the 300 ng/300 μg/kg core group that received the binary mixture of PCB126 and 153 and in a clearly increasing incidence of uterine carcinoma in the 1000 and 4600 μg/kg PCB118 core group and the 4600 μg/kg stop group. In the studies of PCB 126, the tertiary mixture, and the binary mixture of PCB126 and PCB118, no increased incidence of any change occurred in the reproductive systems. The range of changes seen with the different compounds suggests that more than one mechanism may have been involved in promoting the female reproductive pathology. | |||
Hardell, L. et al. 2004 [26] | Case control study where it was analyzed the adipose tissue concentration of HCB, p,p’-DDE, chlordanes and polybrominated biphenyls in 76 cases with endometrial cancer and 39 controls with benign endometrial hyperplasia suggesting an interaction between p,p’-DDE and estrogen replacement drugs in the etiology of endometrial cancer, although no significant associations were found. | |||
Weiderpass, E. 2000 [57] | Case Control study where was measured serum concentrations of 10 chlorinated pesticides and 10 PCB congeners in 154 endometrial cancer and 205 population controls and resulted a no significant associations of increasing levels of pesticide or PCB exposure with endometrial cancer risk. | |||
Sturgeon, S.R. 1998 [54] | Multicenter case-control study: the findings did not support the hypothesis that organochlorine compounds are linked to the development of endometrial cancer. | |||
Adami 1995 [53] | Review that summarizes the evidence regarding whether certain organochlorine compounds increase the risk of breast and endometrial cancers through their estrogenic potential and resulted that no analytic epidemiologic studies of endometrial cancer were published at that data. | |||
Ahlborg 1995 [52] | Review that summarizes the evidence regarding whether certain organochlorine compounds increase the risk of breast and endometrial cancers through their estrogenic potential and resulted that the hypothesis that human exposure to environmental levels or organochlorines would favor an estrogenic overactivity leading to an increase in estrogen-dependent formation of mammary or endometrial tumors is not supported by the existing in vitro, animal and epidemiological evidence. |
Chemical | Pathways of Exposure | Mechanism of Action | Authors (Year) | Results |
---|---|---|---|---|
Bisphenol A (BPA) | Food chain (e.g., plastics in contact with food), consumer products (e.g., dental sealant, plastic additive, etc.) | Estrogen agonists-ER alpha, epigenetic mutations | Wang, K.H. et al. 2015 [61] | The results show that BPA increased growth rate and colony-forming efficiency in a dose-dependent manner, induced EMT and COX-2 gene expression and promoted the migration and invasion ability of RL95-2 cells. |
Gibson, D.A. et al. 2014 [9] | Review that summarizes how BPA is identified as an estrogenic substance and may activate both ERα and ERβ but that activation would be both cell-type- and concentration-dependent. | |||
Rochester, J.R. et al. 2013 [19] | Review shows the associations between BPA exposure and adverse perinatal, childhood, and adult health outcomes, including reproductive and developmental effects, metabolic disease, and other health effects. | |||
Gertz, et al. 2012 [63] | In vitro study where it was demonstrated that BPA and genistein induce thousands of estrogen receptor1 (ESR1) binding sites and change the expression of a subset of genes (more often up-regulated) affected by E2, representing 26% and 6% respectively. | |||
Boehme, et al. 2009 [22] | It was showed a divergent gene expression patterns of the phytoestrogens, as well as weaker estrogenic gene expression regulation determined for the anthropogenous chemicals BPA and o,p’-DDT. | |||
Newbold, R.R. 2007 [59] | There was a statistically significant increase in cystic ovaries and cystic endometrial hyperplasia (CEH) in the BPA-100 group as compared to Controls, suggesting that BPA causes long-term adverse effects if exposure occurs during critical periods of differentiation. | |||
Singleton, D.W. et al. 2006 [25] | It has been relevant how a number of growth- and development-related genes, such as HOXC1 and C6, Wnt5A, Frizzled, TGFbeta-2, and STAT inhibitor 2, were found to be affected exclusively by BPA. | |||
Hiroi, H. 2004 et al. [73] | Human in vivo study suggests the presence of associations between BPA exposure and complex endometrial hyperplasia and endometrial cancer. | |||
Kurosawa, T. et al. 2002 [66] | In vitro study where was performed a luciferase assay on three independent cell lines derived from different tissues transfected with either human ERα cDNA or ERbeta cDNA, indicating that BPA only acts as an agonist of estrogen via ERbeta whereas it has dual actions as an agonist and antagonist in some types of cells via ERα. Thus, the activity of BPA may depend on the ER subtype and the tissue involved. | |||
Bergeron, et al. 1999 [62] | BPA was able to bind to the human uterine ER and to induce both mRNA and protein to levels similar to E2. |
Chemical | Pathways of Exposure | Mechanism of Action | Authors (Year) | Results |
---|---|---|---|---|
Dioxins | Food chain (fat-rich food, e.g., milk and derivates, fatty fish), living environment | Aril hydrocarbon Receptor interaction leading to altered steroid hormone metabolism and neuroendocrine effects including on thyroid | Yoshizawa, K. et al. 2009 [55] | In vitro study where female adult Harlan Sprague-Dawley rats were exposed for 14, 31 or 53 weeks or for two years to different EDCs including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulting in a marginally or significantly increasing of uterine squamous cell carcinoma rispectively in the 6 ng/kg core and 100 ng/kg stop-exposure groups. |
Jana, N.R. et al. 1999 [112] | In vitro study where it was investigated the mechanism of the response of human uterine endometrial carcinoma cells, RL95-2 (epithelial carcinoma cells of the uterus) and KLE (adenocarcinoma cells of the uterus), to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). RL95-2 cells were highly responsive to TCDD in terms of cytochrome P4501A1 (CYP1A1), cytochrome P4501B1 (CYP1B1), and plasminogen activator inhibitor-2 (PAI-2), whereas KLE cells showed little stimulatory effects only at high doses. | |||
Ricci, M.S. et al. 1999 [119] | In vitro study where it was demonstrated that TCDD exerts its toxic action via the aryl hydrocarbon (Ah) receptor, which induces a battery of xenobiotic-metabolizing enzymes, including the cytochrome P450 isozyme, CYP1A1. TCDD-induced 7-ethoxycoumarin-O-deethylase activity was reduced 75% in cultured human endometrial ECC-1 cells exposed to various concentrations of 17beta-estradiol for up to 72 h, with a half-maximal effective concentration (EC50) of 0.9 nM. | |||
Charles, G.D. et al. 1997 [111] | In vitro study where it was investigate the potential role of TCDD in uterine growth utilizing a human endometrial adenocarcinoma cell line (RL95-2). Western immunoblot analysis showed a maximal induction of cytochrome P4501A1 (CYP1A1) at 1 nM TCDD. Furtherome TCCD significantly increased mRNA levels for interleukin-1beta (IL-1beta) by 6 h, and for urokinase plasminogen activator (uPA) and tumor necrosis factor-alpha (TNF-alpha) by 36 h. | |||
Bertazzi, A. et al. 1993 [120] | Case control study where Seveso Population accidentally exposed to TCDD were followed up for cancer occurrence in 1977–1986. No cases of endometrial cancer was detected. |
Chemical | Pathways of Exposure | Mechanism of Action | Authors (Year) | Results |
---|---|---|---|---|
Cadmium | Food Chain (e.g., refined food as flour, rice, sugar; seafood), cigarette smoking | Estrogen agonist- ER alpha | Eriksen, K.T. et al. 2014 [157] | It was found a positive association between cadmium and endometrial cancer for the women with BMI < 25, whereas an inverse association was seen for the women with BMI ≥ 25. |
Adams, S.V. et al. 2014 [158] | Case control study where it was examined the association between dietary cadmium intake and risk of these cancers in the large: it was found little evidence that dietary cadmium is a risk factor for breast, endometrial, or ovarian cancers in postmenopausal women. | |||
Cho, Y.A. et al. 2013 [159] | The analysis found a positive association between dietary cadmium intake and cancer risk among studies conducted in Western countries, particularly with hormone-related cancers such as the endometrial one. | |||
Akesson, A. et al. 2008 [146] | The results dimonstrated that the Cadmium intake was statistically significantly associated with increased risk of endometrial cancer in all women | |||
Yaman, M. et al. 2007 [160] | The amount of Cadmium found in cancerous endometrial samples were not found to be different than those in noncancerous tissues. | |||
Nasiadek, M. et al. 2005 [143] | In the investigated tissues, the correlation between Cd concentration and age was found, but no effect of menopausal status or smoking habits on Cd level was detected. |
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Mallozzi, M.; Leone, C.; Manurita, F.; Bellati, F.; Caserta, D. Endocrine Disrupting Chemicals and Endometrial Cancer: An Overview of Recent Laboratory Evidence and Epidemiological Studies. Int. J. Environ. Res. Public Health 2017, 14, 334. https://doi.org/10.3390/ijerph14030334
Mallozzi M, Leone C, Manurita F, Bellati F, Caserta D. Endocrine Disrupting Chemicals and Endometrial Cancer: An Overview of Recent Laboratory Evidence and Epidemiological Studies. International Journal of Environmental Research and Public Health. 2017; 14(3):334. https://doi.org/10.3390/ijerph14030334
Chicago/Turabian StyleMallozzi, Maddalena, Chiara Leone, Francesca Manurita, Filippo Bellati, and Donatella Caserta. 2017. "Endocrine Disrupting Chemicals and Endometrial Cancer: An Overview of Recent Laboratory Evidence and Epidemiological Studies" International Journal of Environmental Research and Public Health 14, no. 3: 334. https://doi.org/10.3390/ijerph14030334
APA StyleMallozzi, M., Leone, C., Manurita, F., Bellati, F., & Caserta, D. (2017). Endocrine Disrupting Chemicals and Endometrial Cancer: An Overview of Recent Laboratory Evidence and Epidemiological Studies. International Journal of Environmental Research and Public Health, 14(3), 334. https://doi.org/10.3390/ijerph14030334