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INFLUENCE OF ENDOCRINE DISRUPTING COMPOUNDS (EDCS) ON MAMMARY GLAND DEVELOPMENT AND TUMOR SUSCEPTIBILITY
Citation:
Fenton, S E. AND J. L. Rayner. INFLUENCE OF ENDOCRINE DISRUPTING COMPOUNDS (EDCS) ON MAMMARY GLAND DEVELOPMENT AND TUMOR SUSCEPTIBILITY. Presented at Society of Toxicology, New Orleans, LA, March 6-10, 2005.
Description:
Influence of Endocrine Disrupting Compounds (EDCs) on Mammary Gland Development and Tumor Susceptibility.
Suzanne E. Fenton1, and Jennifer Rayner1,2
1 Reproductive Toxicology Division, NHEERL/ORD, U.S. EPA, Research Triangle Park, NC, and 2 Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC.
Breast cancer risk in women is known to be significantly influenced by genetics and by prolonged exposure to estrogen. However, when all known risk factors and characteristics are considered, more than 50 percent of breast cancer cases remain unexplained. There is a growing body of evidence indicating that exposures to certain toxic chemicals and hormone-mimicking compounds may contribute to the development of breast cancer. Several endocrine-disrupting compounds (EDCs) that act in an estrogenic or anti-androgenic manner are known to alter rodent mammary gland development. Although epigenetic in nature, these xenobiotics may hasten development of the gland and increase the incidence of mammary tumors if they significantly alter serum estradiol levels, or if they change receptor expression patterns, hormone transport, or metabolism that results in altered response to endogenous estradiol levels. Nonylphenol is an example of an EDC that this research group has shown to hasten mammary gland development following acute in utero exposure.
Delayed development of the mammary gland also can be caused by in utero exposure to EDCs, resulting in imprinting, or irreversible effects in the offspring. This type of delayed glandular development could lead to increased tumor formation due to a shift or enlargement in the window of sensitivity to carcinogens. For example, a toxicant may delay mammary development so that undifferentiated or dividing cells may be present for longer periods of time, thus rendering the tissue more vulnerable to a subsequent genotoxic insult. The herbicide atrazine and the polyaromatic hydrocarbon dioxin are examples of compounds that delay mammary gland development and increase the potential for mammary carcinogenesis. A delay in mammary gland development has been detected as early as postnatal day 4 and persists throughout puberty in female rats prenatally exposed to atrazine. Similarly, dioxin exposure on gestation day 15 causes an irreversible modification in epithelial migration and branching patterns. Because of altered epithelial differentiation, terminal end buds are present for a longer period of time. These multilayered structures are sensitive to carcinogens, such as 7,12-dimethylbenz[a]anthracene, and exposure to such agents during this critical window of susceptibility could lead to increased multiplicity or decreased latency to tumor formation.
(This is an abstract of a proposed presentation and does not necessarily reflect EPA policy)