Environmental estrogens, such as PCBs, phthalates, and alkylphenols increase estrogen-responsive growth in vitro. This could play a role in the increase in breast cancer incidence witnessed in developing countries since the industrial revolution. The objective of this study is to examine the carcinogenicity of the environmental estrogen, 4- nonylphenol, in a transgenic mouse model (MMTVneu) with a high propensity for developing primary tumors of the mammary glands and metastasis to the lung. Mice will be treated with 4-nonylphenol for 180- 200 days and then euthanized. Tumor incidence, number, proliferation and metastasis will be compared between treated and untreated mice to determine 4nonylphenol's effects on these parameters. Once a month during the study and following euthanasia, blood will be drawn and circulating estradiol levels will be examined for alterations caused by 4- nonylphenol. Primary tumor tissue will be collected following euthanasia and examined for changes in cell cycle kinetics and production of estrogen response genes such as pS2 and TGFA3. Since 4nonylphenol has significantly greater effects on estrogen-responsive transcription than its estrogen receptor affinity would suggest and it alters steroidogenic P450 levels, it is our theory that 4-nonylphenol alters estradiol metabolism, inactivation and elimination. Therefore, livers will be collected from the mice and estradiol hydroxylation and conjugation will be investigated. Overall, the purpose of this study is to examine 4-nonylphenol's effects on breast cancer growth and its mechanism of action on the mammary tumor.
| Acevedo, Ricardo; Parnell, Pamela G; Villanueva, Hugo et al. (2005) The contribution of hepatic steroid metabolism to serum estradiol and estriol concentrations in nonylphenol treated MMTVneu mice and its potential effects on breast cancer incidence and latency. J Appl Toxicol 25:339-53 |
| Baldwin, William S; Roling, Jonathan A; Peterson, Sean et al. (2005) Effects of nonylphenol on hepatic testosterone metabolism and the expression of acute phase proteins in winter flounder (Pleuronectes americanus): comparison to the effects of Saint John's Wort. Comp Biochem Physiol C Toxicol Pharmacol 140:87-96 |
