) Estrogen is a player in the genesis of a number of cancers including cervical, breast, and endometrium. The goal of this application is to reduce the anti-estrogen enhancement of transformation of target cells with diet, thereby preventing many of these cancers. Cervical cancer is a particularly good model because cells infected with certain papilloma viruses are at high risk for transformation The hypothesis of this application is that weak or anti-estrogens, competing with potent estrogens, can prevent estrogen enhancement of cancer promoting activities. Certain dietary compounds induce enzymes that cause more estradiol to be metabolized to anti-estrogens. Phytoestrogens found in many foods are themselves weak estrogens. The hypothesis will be tested in in vitro and in in vivo models for cervical cancer. Weak and anti-estrogenic compounds will be evaluated for their ability to reduce cancer promoting activities of estrogen in cells infected with high risk papilloma viruses. The anti-estrogen metabolite, 2-hydroxy estrone will be used to compete with the potent estrogen metabolite 16a-hydroxy estrone. Indole-3-carbinol, a constituent of cruciferous vegetables, and omega-3 fatty acids will be used to induce 2-hydroxy estrone. The phytoestrogens genistein and equol, from soy will be used as competing weak estrogens. Transcription of papilloma viruses oncogenes, proliferation of cells and acquisition of anchorage independent growth will be evaluated. Dietary indole-3-carbinol will be tested in a mouse transgene papilloma virus model for the ability to reduce estrogen induced cervical dysplasia and/or cervical cancer. Results should establish ways to reduce estrogen associated transformation. Results will also establish whether or not the relative amounts of weak or anti-estrogens to potent estrogens determine the activity of estrogen.
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