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NOVEL EFFECTS OF DIOXIN ON BREAST DEVELOPMENT, FUNCTION, AND SUSCEPTIBILITY TO CANCER
Citation:
FENTON, S. E., J. T. HAMM, L. S. BIRNBAUM, V. RICHARDSON, AND G. L. YOUNGBLOOD. NOVEL EFFECTS OF DIOXIN ON BREAST DEVELOPMENT, FUNCTION, AND SUSCEPTIBILITY TO CANCER. Presented at EDC Forum of the 2005 Endocrine Society Meeting, San Diego, CA, June 03, 2005.
Description:
Breast cancer is the most common type of non-dermal cancer among women in this country. Breast cancer risk in women is known to be significantly influenced by genetics, but over 70% of the women that are diagnosed with breast cancer have non-inherited or sporadic cancer. The risk of breast cancer is thought to be modified by lifestyle and environment. There is a growing body of evidence suggesting that exposures to certain chemicals and hormone-mimicking, or endocrine disrupting compounds (EDCs) may contribute to increased incidences of breast cancer, as well as precocious puberty in the U.S. Our lab and others are studying effects of EDCs on mammary gland and pubertal development in rodents. These studies indicate that EDCs with estrogenic or anti-androgenic activity alter mammary gland and pubertal development in the rodent model. A working hypothesis is that EDCs that alter development of the mammary gland could potentially 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 hormones or growth factors.
Delayed development of the mammary gland can result from in utero exposure to EDCs. For example, evidence from several labs indicates that the polyaromatic hydrocarbon 2,3,7,8- tetrachlorodibenzo-p-dioxin delays mammary gland development in the rat model and increases the potential for mammary tumor development. A delay in mammary gland development has been detected as early as postnatal day 4 and persists into adulthood in female rats exposed to dioxin on gestation day 15. A single exposure, during what may be a critical period of fetal development, causes an irreversible modification in mammary epithelial migration and branching patterns. Because of altered epithelial differentiation, terminal end buds are present for a longer period of time. Several labs have shown that these multilayered structures are sensitive to carcinogens, and exposure to these agents during this period of sensitivity leads to increased multiplicity of tumors or decreased latency to mammary tumor formation. Dioxin has also been shown to alter mammary differentiation in the pregnant mouse and her female offspring, as well as mammary development of rats in multiple generations. These effects of dioxin on the mammary gland and reproductive system of the female rodent may shed light on important periods of development with regard to risks of mammary tumor susceptibility. A recent human study showed that environmental exposure to dioxin-like substances was associated with delayed breast development in young women. Whether these women are at increased risk of breast tumors later in life remains to be determined.
(This is an abstract of a proposed presentation and does not necessarily reflect EPA policy)