This proposal is a request for financial support for a one day symposium on Mechanisms of Estrogen Carcinogenesis to be presented at the American Chemical Society national Meeting, Chicago, IL, Aug. 26-31. There is a clear association between excessive exposure to synthetic and endogenous estrogens and the development of cancer in several tissues including breast, endometrium, liver, and kidney. Besides heredity, the known risk factors for women developing these cancers are all associated with longer estrogen exposure: early menses, late menopause, and long term estrogen replacement therapy. The mechanism(s) of estrogen carcinogenesis is not known. The central theme of this symposium is that excessive binding of estrogens to the estrogen receptor and/or the formation of quinoids is an important mechanism of carcinogenesis for endogenous estrogens and certain estrogens present in estrogen replacement prescriptions. The speakers chosen for this symposium are all supported by R01 grants funded by the National Cancer Institute. In addition, the speakers have published peer-reviewed publications in several highly respected journals including those supported by the American Chemical Society. This symposium will explore three potential mechanisms of estrogen carcinogenesis, including 1) excessive binding of estrogens to the estrogen receptor leading to enhanced cell proliferation and/or 2) the metabolism of estrogens to 0-quinones causing either oxidative damage to DNA and/or 3) alkylation of DNA resulting in initiation and promotion of the carcinogenic process. Given the direct link between excessive exposure to estrogens, metabolism of estrogens, and increased risk of breast and endometrial cancer, it is crucial that factors which affect the formation, reactivity, and cellular targets of estrogens and their metabolites be throughly explored. This symposium will address all of these issues and establish key research areas for the future.
