Selected Bibliography

Discussion

-Adami, H., Lipworth, L., Titus-Ernstoff, L., Hsieh, C., Hanberg, A., Ahlborg, U., Baron, J., and Trichopoulos, D. (1995). Organochlorine compounds and estrogen-related cancers in women. Cancer Causes and Control. 6, 551-566.

-Ahlborg, U. G., Lipworth, L., Titus-Ernstoff, L., Hsieh, C., Hanberg, A., Baron, J., Trichopoulos, D., and Adami, H. (1995). Organochlorine compounds in relation to breast cancer, endometrial cancer, and endometriosis: an assessment of the biological and epidemiological evidence. Critical Reviews in Toxicology. 25, 463-531.

-Anderson, E., Clarke, R. B., and Howell, A. (1998). Estrogen responsiveness and control of normal human breast proliferation. Journal of Mammary Gland Biology and Neoplasia. 3, 23

-Ashby, J., Houthoff, E., Kennedy, S. J., Stevens, J., Bars, R., Jekat, F. W., Campbell, P., Miller, J. V., Carpanini, F. M., and Randall, G. L. P. (1997). The challenge posed by endocrine-disrupting chemicals. Environmental Health Perspectives. 105.

-Bennie, D. T. 1999. Review of the environmental occurence of alkylphenols and alkylphenol ethoxylates. Water Quality Research Journal of Canada. 34(1):79-122.

-Brix, Rikke, Hvidt, Søren and Carlsen, Lars. (2003). Solubility of nonylphenol and nonyphenol-ethoxylates: On the possible role of micelles. Chemosphere. 44(4): pp.759-763.

-Brown, N. M., and Lamartiniere, C. A. (1995). Xenoestrogens alter mammary gland differentiation and cell proliferation in the rat. Environmental Health Perspectives. 103, 708-713.

-Cavalieri E, Chakravarti D, Guttenplan J, et al (2006). "Catechol estrogen quinones as initiators of breast and other human cancers: implications for biomarkers of susceptibility and cancer prevention". Biochem. Biophys. Acta. 1766(1): 63–78.

-Colborn T. (1993) Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environmental Health Perspectives. Oct;101(5):378-84

-Davidson, N. E. (1998). Environmental estrogens and breast cancer risk. Current Opinion in Oncology 10, 475-478.

-Davis, D. L., Bradlow, H. L., Wolff, M., Woodruff, T., Hoel, D. G., and Anton-Culver, H. (1993). Medical hypothesis: Xenoestrogens as preventable causes of breast cancer. Environmental Health Perspectives. 101, 372-377.

-Ford, James, M.D., Plevritis, Sylvia, PhD. (2002) Genetic Alterations in MRI Screen-Detected Breast Lesions. Breast Cancer Research and Treatment. 7651; pp.618

-Ferguson, P. Lee, Iden, Charles R., and Brownawell, Bruce J. Analysis of nonylphenol and nonylphenol ethoxylates in environmental samples by mixed-mode high-performance liquid chromatography–electrospray mass spectrometry. (2001) Journal of Chromatography. 938(1-2); pp.79-91.

-Ginsburg S., Elizabeth, Xiaoying Gao, Brian F. Shea, Robert L. Barbieri. Half-Life of Estradiol in Postmenopausal Women. Gynecol Obstet Invest. 1998(45):45-48

-Guenther K, Heinke V, Thiele B, Kleist E, Prast H, Raecker T. (2002) Endocrine disrupting nonylphenols are ubiquitous in food. Environ Sci Technol. Apr 36(8):1676-80.

-Hoyt P.R., M. J. Doktycz, K. L. Beattie and M. S. Greeley. (2004) DNA Microarrays Detect 4-Nonylphenol-induced Alterations in Gene Expression During Zebrafish Early Development. Ecotoxicology. 12: 469-474

-Jacquez, Geoffrey M. and Greiling, Dunrie A. (2003) Local clustering in breast, lung and colorectal cancer in Long Island, New York. Int J Health Geogr. 2; p.3.

John, E. M., and Kelsey, J. L. (1993). Radiation and other environmental exposures and breast cancer. Epidemiologic Reviews 15: 157-162.

-Kim, Celline & Chopra, Priya. (2008) ‘The Regulation of B-amyloid via Morphine and Estrogen’. (Unpublished research)

-Kortner, Trond M. and Arukwe, Augustine. (2007). The xenoestrogen, 4-nonylphenol, impaired steroidogenesis in previtellogenic oocyte culture of Atlantic cod ( Gadus morhua) by targeting the StAR protein and P450scc expressions. General and Comparative Endocrinology. 150(3):pp.419-429

-Kulldorf, Martin, Feuer, Eric J., Miller, Barry A., Freedman, Laurence S. (1997). Breast cancer clusters in the Northeast United States: A Geographic Analysis. American Journal of Epidemiolohy. 146(2)

-Nimrod, A. C., and Benson, W. H. (1996). Environmental estrogenic effects of alkylphenol ethoxylates. Critical Reviews in Toxicology. 26: pp.335-364.

-Ruthann A. Rudel, David E. Camann, John D. Spengler, Leo R. Korn, and Julia G. Brody. Phthalates, Alkylphenols, Pesticides, Polybrominated Diphenyl Ethers, and Other Endocrine-Disrupting Compounds in Indoor Air and Dust . Environ. Sci. Technol., 37(20): 4543 -4553

-Staples C.A et al. (1999). Measuring the biodegradability of nonylphenol, ether carboxylates, octylphenol, ether carboxylates, and nonylphenol. Chemosphere. 38:2029-2039

-Staples C.A et al. (2001). Ultimate breakdown of alkylphenol ethoxylate surfactants and their biodegradation intermediates. Environ. Texocol. Chem. 20: 2450-2455.

-Vazquez-Duhalt, R., Marquez-Rocha, F., Ponce, E., Licea, A.F., Viana, M.T. (2005). Nonylphenol, an Integrated Vision of a pollutant. Applied Ecology and Environmental Research. 4(1): pp. 1-25.

- Watson, Cheryl S., Bulayeva, Nataliya N., Wozniak, Ann L. and Finnerty, Celeste C.. (2005) Signaling from the membrane via membrane estrogen receptor-α: Estrogens, xenoestrogens, and phytoestrogens. Steroids. 70(5-7): pp.364-371.

Ongoing Research

Conclusion

• 4-NP interferes with genes involved in estrogen signaling and cell proliferation

• ~9% of portfolio genes altered significantly by 4-NP and estrogen

• Supports Teresaka (04) –estrogenicity of industrial compounds

• Half-life of estrogen is 13 hours

• Half-life of 4-NP is 8.2 DAYS (Staples ‘01)

• MCF-7 Breast Cancer Cells

• BRCA1/BRCA2

• 4-NP up regulates the BRCA genes**

** BRCA genes repair DNA + control cell proliferation

Future Work• Effects of other environmental endocrine disruptors

• Short term v. Long term effects of 4-NP

• 4-NP mimics estrogen

• 4-NP and estrogen induce similar changes in expression of estrogen-signaling genes

• 4-NP increases breast cancer risk

Increase BRCA genes

Suspect tumorigenesis

BRCA1 is up regulated by 4-NP at every single concentration. The Environmental Protection Agency (EPA) has stated that the “safe” value of 4-NP in the environment is around 7nM. However, our results show that even 3nM 4-NP induces immediate effects of MCF7 cells.

The first gel electrophoresis relating to the BRCA genes. Results represented by the graph on the left.