Acceleration of mammary neoplasia in aromatase transgenic mice by 7,12-dimethylbenz[a]anthracene

Our studies using the aromatase transgenic mice model have shown that early exposure of mammary epithelium to in situ estrogen as a result of overexpr ession of aromatase predispose mammary tissue to preneoplastic changes. Her e, we hypothesize that the preneoplastic changes induced by mammary estroge n in aromatase transgenic females may be susceptible to environmental carci nogens like 7,12-dimethylbenz[a]anthracene (DMBA), and may result in the ac celeration and/or increase in the incidence of breast cancer. Results prese nted in this study show that tumors appeared in 25% of the mice that were: treated with DMBA and all treated transgenic animals had microscopic eviden ce of neoplastic progression. Control non-transgenic females did not have s ignificant changes even after treatment with DMBA. Consistent with increase d neoplastic changes in DMBA-treated aromatase mice, we have seen an increa se in the expression of genes involved in cell proliferation and cell cycle . We have also seen changes in the expression of oxidative stress markers a nd changes in estrogen-mediated growth factors. These studies indicate that more than one event is required for tumor formation, and that early estrog en exposure leading to preneoplastic changes in the mammary epithelial cell s increases susceptibility to environmental carcinogens that may result in acceleration and/or an increase in the incidence of breast cancer. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.