Estrogen-Induced Depurination of DNA: A Novel Target for Breast Cancer Prevention
Annual rept. 7 Apr 2005-6 Apr 2006
NEBRASKA UNIV MEDICAL CENTER OMAHA
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The COE investigators made outstanding progress in the third year. We found that we can analyze 40 metabolites, conjugates and depurinating DNA adducts of estrogens in the urine and serum of women. The women with breast cancer had high levels of depurinating adducts in the urine, whereas the control women had baseline levels. For the first time, it was demonstrated that E2 induces complete transformation of human epithelial cells with formation of tumors in SCID mice. Furthermore, the ability to characterize cell transformation at the combined levels of the complete genome and the individual gene was determined. The lac I rats showed low mutagenic activity of the mammary tissue when treated with 4-OHE2 and no mutagenicity after treatment with 2-OHE2. The ERKO mice without estrogen receptors, E2 induced tumors in mammary tissue and produced genotoxic metabolites. All these findings provide strong support that estrogens can become genotoxic compounds and eventually initiate breast cancer.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research