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ENVIRONMENTAL TOXICANTS AND DISRUPTED MAMMARY GLAND DEVELOPMENT: THE WINDOW OF SUSCEPTIBILITY
Citation:
ENVIRONMENTAL TOXICANTS AND DISRUPTED MAMMARY GLAND DEVELOPMENT: THE WINDOW OF SUSCEPTIBILITY. Presented at Breast Cancer and Environmental Mutagens, Research Triangle Park, NC, September 22-25, 2001.
Description:
Environmental Toxicants and Altered Mammary Gland Development: The window of susceptibility. Suzanne E. Fenton, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
There are several environmental toxicants known to alter rat mammary gland development and ultimately, tumor formation. Although nongenotoxic, these toxicants may increase tumor incidence via a shift or enlargement in the window of susceptibility to carcinogenesis. 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 subsequent genotoxic insult. Furthermore, disrupted development of the mammary gland can be caused by exposure in utero to xenobiotics, causing an imprinting, or irreversible effect in the offspring. The herbicide, atrazine, and the polyaromatic hydrocarbon, dioxin, are examples of compounds that cause a delay in mammary gland development and an increase in the potential for mammary carcinogenesis. In my laboratory, we have detected a delay in mammary gland development in female Long Evans rat offspring gestationally exposed to atrazine, as early as postnatal day 4 and persisting throughout puberty. 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 multi-layered structures are sensitive to carcinogens, such as DMBA, and exposure to such agents during this critical window of susceptibility could lead to increased multiplicity or decreased latency to tumor formation. We are currently developing a model system to differentiate between direct and developmental effects of toxicants in the mammary gland. (This abstract does not reflect EPA policy).